Assessment of the Psychological State

A psychiatric examination consists of four parts: 1. The psychiatric history 2. Examination of the Mental State 3. Evaluation of the personality 4. The diagnostic formulation The clinical method for history-taking is the interview. The clinician sets out to obtain a comprehensive history in his first interview with the patient. A series of interviews may be necessary before he acquires all the information he needs to understand both how the psychiatric illness came about and why it took the course it did. In his first interview the goal of the clinician is to get at least a preliminary overall history ; in doing so, he will also detect the prominent signs or illness comprising the mental state; moreover, he will have the information enabling him to reach a tentative assessment of the patient’s personality; and he will be able to arrive at a working diagnosis. A diagnosis is an hypothesis about the illness; and about the main aetiological factors operating. It is derived by the clinician from an informed synthesis of the facts elicited. Because diagnosis antecedes therapy, and the clinician will wish to begin the initial treatment after his first interview, he aims to reach his preliminary diagnosis where possible. A first interview takes an experienced practitioner half-an-hour. Subsequent interviews may be briefer, and can be arranged as required to get further information and to extend the psychiatric examination as necessary.

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T h e ir lim ite d a p p lic a tio n so far (as c o m p ared to p o te n tia l uses) has b y an d large co n firm ed this. W h a t sort o f in fo rm atio n do w e h ave , h o w e ve r, on th e social an d stru ctu ral ch an ges that w id esp read m ech an isatio n w ill cause w ith in th e h o sp ital service. O n ly a few , and on th e w h o le in ad e q u ate , atte m p ts to an sw er this q u estio n have been m ade in in du stry b u t th ey can m ayb e p ro vid e som e clues to h e lp avoid dangers an d d isad van tages.
M a n y p e o p le in m e d ic in e have a w ork in g k n o w led g e o f c o m p u te r scien ce.
T h e s e are m a in ly in research w h ilst oth ers arc con cern ed w ith the a u to m atio n o f m e d ic al te ch n iq u e sau to an alysis, au to m a tic E .C . G . read in g, etc. T h e system s an alysts, pro gram m ers an d co m p u te r operators m u st in e v ita b ly co m e from in d u stry. F irm s are alread y p ayin g very high salaries to en sure that th ey get e n ou gh c o m p u te r staff, b earin g in m in d that the N a tio n a l C o m p u te r C e n tre exp ects 5000 co m p u ters to be in use in 19 7 0 , d o u b lin g to 10 ,0 0 0 in 19 7 5 . I f en ou gh co m p u ter p e o p le arc to be attracted to m e d ic in e , th ey m u st be offered h ig h salaries. Jo b in te re st is also im p o rtan t fo r it is show n in in d u stry th at these sp ecialists take a d v a n tage o f the ease o f m o b ility b etw e e n d iffe re n t fields to w id e n th e ir exp erien ce.
If in d u strial lin e-m anagers can ro u g h ly be co m p ared w ith h o sp ital ad m in istrato rs, as re sp o n sib le fo r th e d ay to day ru n n in g o f the h o sp ital services, e xp e rie n ce has sh ow n that tw o situ atio n s m ay arise: the ad m in istrato rs m a y resist an y ch an g e lik e ly to en d an g e r their w ork satisfactio n or p o sitio n , b y m a k in g th eir exp e rie n ce an d a d m in istrative kn o w le d g e re d u n d an t, or th ey m ay fail to exert p ro p e r c o n trol over the p erio d o f ch an ge. T h is last case w ou ld n o t be so great a d an ger if co m p u ter te ch n o lo gists w ere aw are o f th e social turm oil th at th e ir in n o v atio n s can b rin g w ith in a stru ctu red system such as th e h o sp ital service. R e su lts of b io ch e m ical screen in g at Q u een E liz a b e th H o sp ita l, B ir m in g h a m , that " in up to 8 % o f p atien ts a b norm al results fo r tests th at w ou ld not u su ally have b een requ ested led to d iffe re n t or a d d ition al d iagn o se s," m ay, fo r e xam p le , p o in t to the en d o f selectiv e testin g. C h a n g e s n eces sary fo r e le ctro n ic data p ro cessin g w ill affe ct p e o p le 's roles, sa tisfa c tio n , an d e m p lo y m e n tco n su ltan ts, h o u se m e n , nurses, clerical staffin w ays as yet u n kn o w n .
T h e case fo r a n ew typ e o f m ed ical scien tist, th e m e d ical co m p u ter te ch n o lo gist, trained in both c o m p u te r scien ce an d the special p ro b lem s o f m e d ic in e w ou ld seem to b e strong. W h o is to train them is less ob vio u s. L e t u s h o p e , h o w ever, that the p itfa ll w ill b e avo id ed , as it h as n o t alw ays been in the past, of a tte m p tin g to train every m ed ical stu d e n t to be fu lly p ro ficie n t in this re latively new scien ce. INTRODUCTION A psychiatric exam ination consists of four parts : 1. T h e psychiatric history 2. Exam ination of the M en tal State 3. Evaluation of the personality 4. T h e diagnostic form ulation T h e clinical m ethod for history-taking is the interview. T h e clinician sets out to obtain a com prehensive history in his first interview with the patient. A series o f interviews may be necessary before he acquires all the inform ation he needs to understand both how the psychiatric illness came about and why it took the course it did. In his first interview the goal of the clinician is to get at least a pre lim inary overall history; in doing so, he w ill also detect the prom inent signs or illness com prising the m ental state; moreover, he w ill have the inform ation enabling him to reach a tent ative assessment of the p atient's personality; and he w ill be able to arrive at a working diagnosis. A diagnosis is an hypothesis about the illness; and about the main aetiological factors operating.
It is derived b y the clinician from an inform ed synthesis of the facts elicited.
Because diagnosis antecedes therapy, and the clinician w ill wish to begin the initial treatm ent after his first interview, he aims to reach his prelim inary diagnosis where possible. A first interview takes an ex perienced practitioner half-an-hour. Subse quent interviews m ay be briefer, and can be arranged as required to get further inform ation and to extend the psychiatric exam ination as necessary.
A theoretical knowledge of interviewing procedure is essential, but is not sufficient. Psychiatric interviewing is a practical skill which can be learnt only through actual ex perience with real patients.
Furtherm ore, regular supervision is needed if technical errors are to be identified and progressively corrected. A n invaluable aid is provided by the use of video-tape; the trainee interviewer has his psychiatric exam ination of the patient tele vised, and when re-played subsequently he and his instructor have the actual clinical data before them for review.
A nother im portant training m ethod is ob tained from w atching experienced interviewers at work.
W h en conducting a psychiatric examination the clinician inevitably makes use of his own personality: he relies on his own capacity for com m unication. H e seeks to gain an objective view of the extent to which he succeeds in expressing him self as he intends. His instruc tor and such aids as tape recording and tele vision show him if he is accurate in his im pression about the way he affects people.
T o conduct a psychiatric exam ination two chairs arc needed, placed more or less at right angles. The clinician and his patient are then free to look at one another when they wish, without imposing any requirement for fixed stares, as would be suggested if the two chairs were facing. (A directorial station behind the office desk is of course altogether inappropri ate.) The room should be quiet and inter ruptions minimal.

THE CLINICIAN'S APPROACH
A question-and-answer technique which may serve, for example, in a general medical exam ination is not desired. The psychiatric history should flow smoothly from one topic to a related one, in a sequence meaningful to the patient. The clinician acts as a catalyst. His primary function is to assist the patient to generate a clinically useful account of personal experience. The clinician writes steadily, to obtain an accurate, factual and full record of the interaction. Any questions he asks are noted as well, so that the verbal stimuli offer ed to the patient are also recorded. A good history is neither nebulous nor abstract. W h e n the patient mentions somebody, that person should be named, e.g. " I was going with a man friend at that time" . The clinician asks, "W h a t was his first name?" This is then re corded; if this person again enters the patient's account, in the present or a later examination, he can be rapidly identified and related to the earlier information.
The competent clinician does not take the patient firmly in a dull routine through each step in the sequence of historical areas. He leaves the patient relatively free to reflect, to overcome hesitations, to go back and amplify, and to alter earlier statements as confidence is established. The clinician gently guides the patient, advises him when inconsequential de tail threatens to crowd out important events and indicates quite frankly when he thinks the patient is following a blind alley. The clin ician's task is to gain possession of the neces sary facts in each of the crucial areas.
This apparent discussiveness is easier to permit the more experienced the clinician becomes. It is appropriate for him to indicate quite plainly to evasive patients that he must have the necessary information. He does not need to encourage the patient with phrases of approval or expressions of sympathy. It goes without saying that he never conveys moral censure or disapproval, although unwittingly clinicians sometimes do. He has no call to become autobiographical himself, and tell the patient about his own trying experiences, child rearing practices, or opinions and attitudes.
In the course of the examination the matters about which people are sensitive can be dealt with sensibly and directly as technical data. Behaviours usually regarded as wrong or un usual can be broached without equivocation, no suggestion of moral evaluation entering, e.g. " H ave you tried to end your life?" Such an enquiry may be welcomed by a depressed patient as a much needed opportunity to dis close painful impulses towards suicide; in the process, speaking about the suicidal intention may effectively serve to deter the patient from making a suicide attempt. Sexual experience is discussed in terms which the patient is sure to understand, checking where necessary the patient's term for a part of the body or a sexual activity.
The contemporary patient will almost certainly know what "masturb ation" means, but not inevitably; often the clinician will perceive that more explicit ex planations or simpler words are needed to obtain the information he seeks.
W h ile the patient is not constrained to give a formal, choronological and precisely sequen tial account, the clinician examining the psychiatric patient has a technical task to carry out, a schedule of operations to be performed. This he aims to carry out as methodically as he would examine any other clinical sector, the neurological system, for example. If he has not examined the fundus he will be aware of this omission, and if he neglects to test the plantar responses the trained clinician likewise knows that his examination is incomplete. Similarly with the psychiatric assessment. If the clinician has not found out about the patient's father, his understanding of the patient's personality is the poorer; if the patient's job record has been neglected, the history is also incomplete.
The psychiatric examination is a technical skill, within the competence of all clinicians, and is not in any way a nebulous or impressionistic procedure. O ne can know about a person's m ind with more or less certainty according to one's ability to carry out the relevant clinical procedures. THE PSYCHIATRIC HISTORY i . The Description of the P atie n t: The patient's name, age, occupation, marital status, sometimes his religious affiiliation andfinally -the method of his referral are facts the clinician will want to record. Eliciting such relatively neutral information may be a useful way of starting the history-taking; the patient is able as he replies to settle in his chair as com fortably as possible, and to assess the situation he finds h im self in. T h e patient also needs an opportunity to size up the clinician as the exam ination begins.
2. T h e Reasons for the C onsultation : T h e clinician then ascertains why the patient has com e, and what the patient requires o f him . T h e p atient's reason for the interview m ay on occasion be straightforward and at times bizarre. T h e m ythical patient who requests a certificate of sanity wants the clinician to study his mind and then pronounce on its stability. T h e police m ay send a patient and be equally explicit -e.g. as occurs when a psychiatrist is asked to exam ine a woman who has harmed her children physically and has then attem pted to kill herself. It m ay be a relative who brings the patient, as occurs when a m other tells the clinician she has been wor ried recently about her small son, and de scribes m annerism s which alarm her.
T h e presenting reason for the referral o f course may be m erely the introductory gam bit, to be extended when the clinician has gained the p atient's confidence: a man com plaining in itially o f indigestion m ay later confess that he has actually com e on account of im potence.
3. T h e P resent Illn e s s : H aving established why the patient has requested to be seen, the clinician then obtains a detailed account of the patient's sym ptom s. Each com plaint is to be recorded scrupulously, in terms close to the p atient's own. If the patient mentions a pain in the heart, that is to be recorded as his sym ptom ; it should not be translated into clinicalese, such as " praecordial pain" . If the clinician rephrases the patient's actual selfdescription into clinical jargon he sacrifices veracity and impairs his own grasp of the patient's experience o f illness. An adequate description of the illness has been reached when the clinician has traced chronologically each m anifestation of the disorder.

4.
T h e F am ily H istory consists of a verbal sketch by the patient of both his parents and of all his brothers and sisters. " Y o u m ention ed your father -w hat sort of person is h e?" T h e question causes som e patients to pause in perplexity, until after hesitation they describe the father as one of the best, or portray him as strict but perfectly fair, or as a mean man who terrorized the fam ily when drunk at week ends.
T h e clinician can usually gather w hether the father was perceived positively, in a neutral light, or negatively. T h e im port ance o f this inform ation is that it conveys the role a parent took in a p atient's personality form ation: a parent is incorporated during growing-up, and constitutes an inner psycho logical representation form ing an aspect of the patient's self.
T h e m other often is characterized with less trouble. Patients fairly readily say w hether she was kind and gentle, or two-faced, or a virago who started her persecution before the p atient's birth by striving to abort herself. A gain, in describing his m other the patient is disclosing a significant relationship which contributed to his character structure.
H is position in the sibship m ay be im port ant. If he was an only child, alone with his m other until five years of age when his father was dem obilized from the army, then to have a baby sister arrive on the scene, the patient m ay proceed to describe a rivalry which agit ated his childhood and coloured his subsequent adult social relationships with envy and com petitiveness.
T h e size of the sibship is obviously relevant. T h e clinician's perception of the parental fam ily is filled out when the patient is asked to com m ent on the general atm osphere which existed in the hom e. 5. T h e personal history can follow naturally from the account o f the parental fam ily. T h e clinician finds out if the patient thought he was a wanted child, avoiding the pitfalls of asking about breast-feeding and toilet-training when the patient is both in the dark about these early circumstances and also mystified regarding their relevance to his present distress. T h e clinician will naturally want to know w hether the patient acquired control of his sphincters at the usual age, whether he bit his nails, and stopped using tem per tantrums as a means of attem pted mastery of the house hold -but these crucial facts are seldom elicited by blunt questions. T o grasp in add ition whether the patient separated from his m other w ithout difficulty and managed to start his school attendance w ithout anxiety, whether he had an early conduct disorder like stealing, or an early neurotic illness such as a child hood obsessional state, calls for an ability on the part of the clinician to em pathize with the patient, and to achieve this so accurately that the patient realizes the level of perceptiveness obtaining.
O ne then discovers from the patient about the onset of puberty, the developm ent of his sexual awareness and inform ation, and the form of his erotic imagery.
H e conveys whether he had a chum , a first close friend ship. His progress at school is studied. T h e course o f his adolescence discloses whether he was able to separate off gradually as an independent individual from his parents, and whether this social growth -if it occurred appropriately -was relatively untroubled, or took the form of a disruptive rebellion. Identity-form ation proceeds rapidly from the m iddle teens, and if arrested the youngster does not arrive at an understanding of his personal potentiality, nor a decision about the work he is fit for, nor a definition o f the values he wants to advance.
H e m ay be greatly troubled about sexual aspects o f this stage of m aturation, with prolonged and recurrent fears about hom osexuality or m asculine in feriority.
T h e girl m ay reject aspects of fem ininity.
In the later teens the capacity for close relation with another person begins to develop if personal m aturation is sufficiently orderly, the individual finding greater purpose when in intim ate association with som ebody else.
T h e clinician then inquires about courtship, m arriage and the p atient's own children. H e com pletes the account o f the personal history by follow ing the jobs the patient has had during the course of his working life.
6. Previous Illnesses are then studied. Phys ical illnesses arc described m ore readily b y the patient. O ne is not so closely associated with one's body as with one's psychological state, therefore past som atic disorders and hospital ization can be rapidly surveyed. (T h ey are often not accurately rem em bered). Physical disorders, quite apart from their som atic ex pression, can o f course have em otional con sequences, especially if they occurred early in life or left a handicap which interfered with the p atient's social participation.
Previous psychological disorders are som e times m ore difficult to track down. T h e y are often revealed if careful questioning is direct ed to the m ajor stressful epochs in the bio graphy; the start o f schooling, puberty, later adolescence, courtship, m arriage, and the onset of m iddle life when youthful perspectives have outrun their applicability. T h e past psychi atric disorders and the way they were m an aged are recorded in order of occurrence. 7. T h e previous personality is especially im portant when the patient has a serious illness, a psychosis. T h e onset of psychosis m ay con stitute a break with the p atient's form er self. Suddenly, out of the blue, the delusion took form ; the cheerful, busy man altered to be com e anxiously preoccupied and troubled by convictions that he suffered from cancer.
T h e previous personality is im portant not only to define the tim e of onset of illness. It is also im portant because from his under standing of it the clinician can identify especial strengths -perhaps obscured b y the sym ptom s o f illness -w hich the patient w ill be able to call on when recuperating: values and habits of m ind, degree o f initiative, friend ships and other social relationships, m em ber ship of groups, clubs and organizations, and special interests.
As the patient speaks the clinician writes. H is transcript o f the interview m ay not be orderly, but were he to cast his m aterial in system atic form he would have obtained data in each of the im portant sectors o f the p atient's biography.
The second p a n of this article will appear in the next issue of R es M edica.

T r i a l b y f i r e
T h e C h ie fs being m et, a hurdle or a kind of wooden gridiron is fixed about an ell from the ground, sufficiently large and strong to receive the body o f a m an. T h e candidate places him self on this couch, lying on his back, putting into his m outh a hollow cane which is to serve him in breathing; then they cover him entirely and closely with plantain leaves, observing to pierce those that are over his head so that his cane m ay pass through them. A fire is then kindled under him , so managed that the flame shall not reach the grate but m ay give enough heat to broil their ignorant victim . If he endure the whole patiently and unm oved, he is saluted as one of their Caliques.
-from a D issertation read befo re the So ciety in 1 7 85.

Coronary
Heart Disease is there a treatm ent for the patient 'at risk' ?

C L O F IB R A T E T R A D E M ARK
allows you to take positive action because Atrom id-S (a) brings down blood lipid levels (b) corrects throm bogenic abnorm alities Side effects are minimal and infrequent and the treatment is easy to take indefinitely. Thousands  It has been variou sly described as occu rrin g in 6 % , 8 % , 1 0 % , 1 2 % and 2 0 % o f patien ts w ith m yo card ial in fa rc tion.
S h o ck acco m p an ies th e onset o f pain in fe w eases and m o st cases o ccu r in the first tw en ty-fou r hours a fte r in farctio n alth o u g h they m ay o cc u r several days after.

CLINICAL CRITERIA
T h e criteria fo r diagnosis o f shock m ay vary w ith d iffe re n t au th ors (h en ce the an om alo u s 2 0 % ab ove) b u t, in gen eral, it is agreed that shock is suggested c lin ically b y the fo llo w in g featu res: cold , clam m y extrem ities, p allo r and cyan osis, rap id , th read y p u lse, anu ria or o lig uria, an xie ty, restlessness or a p ath y, an d p ro longed h yp o te n sio n . T h e o n ly o b je ctiv e assess m e n t is o f blood pressure and this alo n e does n o t d efin e shock. C o n sid e ra b le variatio n m ay th erefore b e exp e cte d in diagnosis.
In view o f the difficu lties in d e fin in g the criteria fo r diagnosis o f sh ock, the in d ivid u al criteria and the in te rp retatio n s placed upon them w arran t fu rth e r discussion.
T h e p allor, cold ness, clam m in ess and o lig uria are taken to in d icate an in crease in activity o f th e sym p ath e tic nervou s system lead in g to sw eatin g and a redu ction in b lo o d flow to the skin an d the kid n e y resp ectively.
S im ilarly, signs o f an xie ty, restlessness or a p ath y are taken to in d icate a redu ction in cereb ral b lo o d flow or cerebral h yp o xia. A n x ie ty or restless ness m ig h t be e x p ec ted in patien ts w h o arc in pain an d ap p reh en sive o f th e ir m ortal fu tu re. A d e q u a te m eth o d s fo r the m e asu rem en t o f arm an d cerebral b lood flow exist b u t the m easu rem en ts d o n o t ye t ap p ear to h a v e been m ad e in card io g en ic sh ock. T h e tachycardia also reflects the increased activ ity o f the sym p ath o-ad renal system , the increased rate b ein g due p ro b ab ly to an increase in sym p ath etic activ ity to the h eart and to the high level o f b lo o d catech o lam in es in shock. T h e in crease in urin ary n orad ren alin e an d ad ren alin e w h ich has b een dem on strated after m yocard ial in farctio n appears to b e related to th e clin ical severity o f the co n d itio n . T h e th read y pulse m ay b e taken as an in d icatio n o f th e redu ction in stroke vo lu m e. C yan o sis represents an increase in the am o u n t o f redu ced h aem o glo b in visib le in the su b -papillary ven ous plexuses and is in flu enced by the h aem o glo b in co n ten t o f the b lo o d . Socalled cen tral cyanosis is said to represen t an arterial oxygen saturation o f less than 9 0 -9 5% b u t trained clin ical observers are un an im ou s in th eir ob servation on ly w hen the oxygen saturation o f blood is as lo w as 7 5 % . T h e m isle ad in g effects o f fluorescent lig h tin g are im p o rtan t. Su ch cyanosis m ay be d u e to in ad e q u ate p u lm o n ary o xyg en atio n , in creased d eo xyg enation o f arterial b lo o d or v e n o arterial sh u n ts. A ll three m ay be im p o rtan t in card iog en ic shock.
H yp o te n sio n is d ifficu lt to d efin e in view o f the w id e range o f norm al blood pressures in the general p o p u latio n . In d ire ct m easu rem en t o f b rach ial systolic blood pressure w ith a sp h yg m o m an o m e te r com pares fav o u rab ly w ith dire ct intra-arterial record in g (at least at norm al levels o f b lood pressure) w ith in certain lim it atio n s, e.g., c u ff w id th and le n g th . W h e th e r the agreem en t is o f the sam e order in h yp o tension is n o t recorded.
A systolic blood pressure o f less than 10 0 m m . H g. or less than 9 0 m m . H g. has been taken as in d icatin g shock w h ile others feel that a systolic b lood pressure o f less than 80 m m . H g. is a necessary criterion o f shock. O th ers again ad h ere to 80 m m . H g. w ith an " a llo w an c e " o f 90 or 10 0 m m . H g. for previou sly hyp erten sive patien ts.
M u tu al agreem en t ab o u t the valu e o f blood pressure taken to in dicate shock is desirable if thera p eu tic trials arc to be com p arable.
H y p o tension in shock can be taken to in dicate that the heart is u n ab le to m ain tain blood pressure b y an ad eq u ate o u tp u t in a situ ation w here the total periph eral resistan ce is n orm al or raised. It m u st b e distin gu ish ed from the in itial h yp oten sio n often seen in m yocardial in farction w h ich is relieved by analgesics or sedatives and is attrib u ted to pain . V aso-vagal attacks and excessive doses o f m orphine., p e th id in e or sedatives m ay also be m islead in g causes o f h yp oten sio n .

HAEMODYNAMIC CRITERIA
T h e clin ical defin ition o f shock is n o t e n tirely satisfacto ry and since the early classical studies o f C o u m a n d attem p ts h ave been m ad e to find a h ae m o d yn am ic expression o f shock. R ig h t heart ca th e te risation is essential in h aem o d yn am ic studies if on e is to m easu re cardiac ou tp u t, central ven ous pressure and p u lm o n ary artery pressure. It is used fo r w ith d raw in g sam ples o f " m ix e d " venous blood for d irect F ic k or in jectin g dye fo r dye diffusion estim ation s o f cardiac o u tp u t. C ard iac o u tp u t is trad itio n ally expressed as cardiac index ( L / m in ./ m2) in an atte m p t to elim in ate vari ations in cardiac o u tp u t related to b o d y size. T h e total perip h eral resistance can be calc u l ated from the relation Mean Aortic Pr. -Central Venous Pr.

Total Peripheral Resistance
In anim als the h aem o d yn am ic con sequen ces o f shock have also been studied a fte r coronary em b olisation w ith spores or m icrospheres, coronary ligation or occlusion .
T h e o u tstan d in g featu re o f h aem od yn am ic studies has been the u n iform d em onstration o f a fall in cardiac in dex in card iogen ic shock. It is im p o rtan t to rem em b er that this is an acu te fall in cardiac in d ex. In gen eral, the low er the cardiac in d ex, the m ore severely ill the p atien t is, alth ou gh sp ecific instances h ave recen tly been described w h ere a very lo w car diac index has been p resen t in patien ts w ith ou t shock. H yp o te n sio n itse lf is n o t sufficient to define shock sin ce sym p ath e cto m ised patien ts m ay h ave ad eq u ate tissue perfu sion w ith a slow pulse and a lo w b lood pressure. T o ta l peripheral resistance in sh o ck has been described as b ein g increased, n orm al or decreased. G u n n a r divides his cases in to tw o groups: on e w ith an increased p erip h eral re sistance w h ich is con sidered to represen t the n o rm al reflex response to a fall in cardiac in dex and on e w ith a decreased periph eral re sistance w hich is b elieved to b e the result o f som e vascu lar reflex from the dam aged heart. P atien ts w ith a low total periph eral resistance responded to n orad ren alin e b y in creasing periph eral resistance w hich is taken to in d icate that the vasoco n strictor m echanism is still fu n ctio n al alth o u g h reflex vasoco n striction is in h ib ited b y a reflex from th e dam aged heart. H o w ever, in cats the vascular tree can be re sponsive to noradren alin e in the " sh ock state " lon g a fte r it h as ceased to respond to sym p ath e tic nerve stim u latio n .

REFLEX SHOCK?
T h e heart has m an y receptors. S tim u latio n o f som e o f them m ay lead to h ypoten sio n as, for e xam p le, in the le ft ven tricu lar Bezold-Jarisch reflex w ith v e ratrin e . T h is m ay be the m echanism o f the bradycardia and h y p o te n sion seen in " sh o cked " dogs w h ich is abolished b y vagotom y. P ossib le receptors for such a reflex h ave been described.
A gress has d e scribed an oth er possib le reflex in dogs m e d i ated b y the dorsal sym p ath e tic roots, b u t his attem p ts to id en tify and b lock such a reflex in m an have n o t been co n tin u ed and w ere presu m ab ly un su ccessful.
T h e h ig h er fre q u en cy o f sh ock in patien ts w ith b ranch rather than m ain stem occlusion s in the coron ary arteries has been given as a p ossib le in dication o f reflex m ech an ism s in h u m an card iogen ic shock.
H ow ever, the sign ifican ce o f a reflex from the in jured m yocardium rem ains un-d ete rm in e d . D o g s w ith d en ervated h earts m ay still b e sh o cke d a fte r in fa rctio n . P re su m ab ly p e o p le w ith tran sp lan ted hearts w ill still be liab le to d evelo p sh o ck a fte r m yo card ial in farc tion. T h is and th e slow on set o f sh o ck do not favo u r a reflex m ech an ism .
A n acu te fall in card iac in d e x is th e basic lesion in card io g en ic shock.
S h o c k is n o t associated w ith an y p articu lar size or site o f in farctio n . In o n e stu d y sh ocked patien ts had a h ig h er in cid en ce o f previou s in farctio n than non-shocked p atien ts w h ereas th e p ost-m ortem h earts e xam in ed b y C ro n in in d icated that sh ock cases had a lo w e r in cid en ce o f previous in farctio n .
C ro n in suggests th at a previou s in farct m ig h t p ro tect th e h eart th rou gh the d e ve lo p m e n t o f sign ifican t in ter-coronary an astom oses.
T h e im p a irm e n t o f cardiac fu n ctio n has been b riefly d escribed b y M ac-K e nzie et al. In th eir stu d y m easu rem en ts of m yo card ial p erfo rm an ce in d icated " gross im p a irm e n t" in card io g en ic shock. T h is has sin ce been described b y others. A m ark e d ly in creased alveolar-arterial oxygen tension grad ie n t w as also d escribed an d has been co n firm ed b y others in card io g en ic sh ock and in acu te m yo card ial in farctio n w ith o u t shock. A sig n ifican tly in creased grad ie n t is p resen t even six to tw e lve m o n th s a fte r in fa rctio n . T h e h yp o xaem ia is n o t d u e to in ad eq u ate v e n til atio n sin ce the P a C O 2 is norm al or even de creased in these cases. T h e h yp o xae m ia is due p artly to an in creased p h ysio lo gical dead space; p artly to ven ou s ad m ixtu re an d also in som e p atien ts to the presen ce o f a true sh u n t. T h e distu rb ed ven tilatio n -p e rfusion ratios arc p ro b a b ly d u e, in part, to the fall in cardiac in d ex observed in shock le ad in g to p erfusion changes, an d , in part, to th e increased p u l m on ary ven o u s pressure acco m p a n y in g p u m p failu re lead in g to p u lm o n ary co n gestio n . T h e rise in le ft v e n tricu lar end-diasto lic pressure w h ich is im p lied in the genesis o f p u lm o n ary con gestion and oedem a in card io gen ic sh ock has recen tly b een d em o n strated . D e ta ile d in vestigation o f th e v e n tilatio n -p erfusion ratio ch an ges in d iffe re n t parts o f th e lu n g should be p o ssib le w ith th e tech n iqu es w h ich h ave been d escrib ed , b u t in vestigation s o f this natu re h ave yet to b e carried o u t in card io ge n ic shock. T h e y should d e m o n strate m o re c learly the n atu re o f th e v e n tilatio n p e rfu sio n im b alance.
T h e presen ce o f p u lm o n ary con gestion in c ard io g en ic sh o ck p ro b ab ly d ep en d s p artly on the en th u siasm w ith w h ich it is so u gh t and p artly on th e severity o f the eases described. In d e e d , an increased p h ysio lo gical dead sp ace w as very e vid en t in these p atien ts.
It is in such cases p articu larly that a regional analysis o f ve n tilatio n -p e rfusion ratios w ould prove in terestin g.
T h e true sh u n t w h ich has been described is th o u g h t u n lik ely to be d u e to arterio-venous anastom oses " sin ce it disappeared on recovery in tw o cases" . T h e p o ssib ility o f arterio-venous anastom oses as a facto r in sh u n t at h ig h a lti tude has been described in association w ith an elevated p u lm o n ary arterial pressure b u t no such relatio n sh ip b etw e e n p resen ce o f sh u n t and p u lm o n ary arterial pressure exists a fte r m yo card ial in farctio n . It has been suggested th at the sh u n t m ay b e due to " collapse, oedem a or b lo ck age o f alveoli in som e areas o f the lu n g w h ere there is co n tin u e d c irc u la tio n ." T his is m ore likely.

ACID-BASE BALANCE
T h e h yp o xae m ia o f card iog en ic shock is associated w ith a sign ifican t acidosis due p rin cip a lly to a rise in th e co n cen tratio n o f blood lactate.
K irb y and M c N ic o l n ote that the acidosis fo u n d in acu te m yocardial in farction is m ost severe in patients with hypotension ( < 9 0 mm. Hg.) plus left ventricular failure (? shocked).
T h e demonstrated rise in lactate/pyruvate ratio is indicative of tissue hypoxia and reflects an increase in the oxid ation of N A D H2 by the conversion of pyruvate to lactate in the cycle of anaerobic glycolysis. Anaerobic glycolysis is m ore active in hypoxia because less m olecular oxygen is available for the operation of the cytoch rome system and aerobic glycolysis.
T h e increased m ortality found with severe acidosis is probably causally related and re presents an association between two accom paniments of tissue hypoxia. In man correc tion of the acidosis leads to an increase in blood pressure in non-sh ocked patients but this may have been related to the procedure and to the volume infused. T h e effect of correc tion in shocked patients is not docum ented. O ther reports associate acidosis with arrhyth mias in man, decreased myocardial contract ility in dogs, and vasopressor antagonism in dogs. In dogs the com bination of acidosis and hypoxaemia is particularly lethal: the sur vival rate is increased by correction of both.

CORONARY AND OTHER REGIONAL BLOOD FLOWS
T h e following functional points are also worthy of note. T h e hypotension of shock w ill lead to a significant reduction in coronary blood flow since in the human ease o f infarc tion (but not the dog and hence partly the dubious relevancy of experim ental cardiogenic shock in dogs) the coronary vessels w ill almost certainly be atherosclerotic, arteriosclerotic or even calcified. T h is will lim it or even elim inate any faculty for vasodilatation in response to hormonal, nervous, m etabolic or any other demands. In this situation the coronary flow becomes to a greater or lesser extent depend ent on aortic diastolic pressure since most coronary flow occurs during diastole.
T h e existence of coronary autoregulation is still debated but where demonstrated it probably ceases, like cerebral autoregulation, at pressures of 50-80 m m. H g. T h e effect of degenerative arterial disease on coronary autoregulation is not known and it should be possible to study this in a suitable animal preparation with and without the com plications of myocardial in farction since its effect can only be guessed in man.
Arterial disease is found in a wide range of animals including snakes, lizards, tor toises and vultures. Disease can also be pro duced by altering the diet of rabbits, rats and pigs and this disease closely resembles that found in man. T h e effect of coronary artery disease on autoregulation of coronary blood flow would be most easily studied in the pig. (For sim ilar reasons the pig would seem to be a more suitable animal than the dog for in vestigating the efficacy of different forms of therapy in cardiogenic shock). F o r the m om ent it is agreed em pirically that a pressure of 50-80 mm. H g. is usually adequate to m ain tain coronary and cerebral blood flow. Regional flow studies m ight be interesting here also. I n view of the need for a m inim um blood pressure difficulties arise in therapy (see later) since attem pts to increase the aortic pressure by vasoconstriction to maintain coronary flow will increase the afterload of an already em barrassed heart.
T h e sym pathetic vasoconstriction in shock leads to a reduction in renal blood flow, glom erular filtration rate and urine secretion. If this oliguria (or anuria) is m aintained m icro scopic changes may be visible in the kidney structure.
Sim ilarly im pairm ent of liver function has been demonstrated in acute myocardial infarction which is probably related to hepatic vasoconstriction. T his may be a factor in the lactic acidaemia.

M ICR O CIRCULATIO N
T h e changes observed in the peripheral circulation in shock have been investigated by m any workers.
M icroscopic examination of the microcirculation in shocked animal prepar ations has shown great species variation in the behaviour of the m icrocirculation during shock and it is difficult from the observations which have been made to indicate any con sistent m icrocirculatory defect in shock. H ow ever, disturbances of vasomotion and of the flow patterns in exchange vessels have been observed. T h e role of arterio-venous shunts in the microcirculation remains uncertain.
Coupled with disturbances of flow, pressure and exchange relationships in the m icro circulation m ay be disturbances of the coag ulation mechanism which have been observed in shocked patients by the proponents of a hypothetical mechanism for disseminated intravascular coagulation or sludging. T h is will lead to further disturbance of the exchange and nutritive functions of the m icrocircul ation. If present in cardiogenic shock sludg ing should be visible in the bulbar conjunctiva. M e lla n d e r using his tech n iq u e fo r the in d irect stu d y o f th e m icro circu latio n in cat skeletal m uscle has n o tice d in sh ock a p ro gressive d eclin e in the p re cap illary resistance response to sym p ath e tic n erve stim u latio n w h ile the cap acitan ce response rem ains. H o w ever, u n p h ysio lo gical doses o f n orad ren alin e w ill retrieve the resistan ce response w hen s y m p a th e tic n erve stim u latio n fails. I f shock is p ro lon ged the cap acitan ce response to sym p ath e tic n erve stim u latio n is ab olish ed and in travascu lar p o o lin g m ay occu r. A t the sam e tim e d istu rb an ces o f the relatio n sh ip betw een pre-and post-capillary resistances and h en ce the S tarlin g m ech an ism w ill lead to h a emoco n ce n tratio n . M e lla n d e r in terp reted the re fractorin ess to sym p ath e tic n erve stim u latio n as b ein g d u e to the p resen ce o f tissue h ypoxia and accu m u late d " m e ta b o lite s" . T h e natu re o f such m e tab o lites rem ains un certain b u t acidosis is p ro b ab ly a factor. C a t skeletal m u scle in h ae m o rrh agic shock is n o t the hum an p erip h eral circu latio n in card iog en ic shock b u t com p arison s are useful an d ap p are n tly valid sin ce recen t p u b licatio n s a llo w the fo llo w in g te n tative in terp retatio n of p erip h eral circu lato ry failu re in card iogen ic shock: a fte r in farctio n card iac fu n ctio n is severely im paired an d alth o u g h increased sym p ath o-ad ren al a ctiv ity m ay b e ad e q u ate at first to m ain tain b lood pressure it is later in ad eq u ate. I f the vasoco n striction is severe or p ro lon ged enou gh it leads to tissue h yp o xia and acidosis. H yp o xae m ia w ill exaggerate this p h en o m en o n and total p erip h eral resistance m ay fall. P rogressively th e resistan ce vessels b e co m e refracto ry to sym p ath e tic nervous stim u li w h ile m ain tain in g so m e sen sitivity to n o rad ren alin e.
U ltim a te ly this response also disappears alo n g w ith the cap acitan ce response. T h is m ay lead to acidosis, loss o f cap illary in tegrity, h ae m o co n cen tratio n , stagn atio n , dis ru ption o f lysosom es, co agu latio n o f b lood and tissue destru ction w ith co n se q u en t loss of organ fu n ctio n and death . P ro m in en t am on g the u ltrastru ctu ral ch an ges in sh o ck is m ito ch o n d rial d am age.
T W o u ld ch em ical sym p ath e cto m y sh ow the sam e effect? I f the effect w as b en eficial m ig h t it be ap p lic a b le to hum an cases as a form o f " p re v e n tiv e " tre atm e n t for card io g en ic shock? D o p e o p le w ho have been sym p ath e cto m ise d d e ve lo p card io g en ic sh ock as ofte n as th e rest o f th e p o p u latio n ? I f so, do th ey also have an 8 0 % m o rtality?
T h e seq u en ce o f even ts in sh ock is n ever seen in its u n d istu rbed e n tirety sin ce th erap y is usu ally in stitu ted early in the m

O XYG EN
In card io g en ic shock, the tissue P02 is p ro b ab ly m u ch lo w er than it sh ou ld b e, and P a O 2 is c e rtain ly low . P a C O 2 b ein g essen tially n o r m al, the ad m in istratio n o f 1 0 0 % oxygen is preferred sin ce the P a O 2 o f som e p atien ts m ay be refracto ry to oxygen therapy.
H yp e rb aric oxygen p ro tects again st death from arrh yth m ias in " card io g en ic sh o ck " in dogs and pigs b u t C am ero n has o n ly n oticed a " non -statistical suggestion o f a redu ction in a rrh y th m ia s" w ith such th erap y in m an.

VASO C O N STR IC TO R S
P u re vasoco n strictors such as an gio ten sin have no place in th erap y sin ce they increase b lood pressure b y in creasin g periph eral resist an ce at the expen se o f in creasin g cardiac over load and decreasin g cardiac index.
αβ drugs such as noradrenaline and metaraminol have been used in classical therapy for years. They:-1. act in small doses to increase myocardial contractility and cardiac index, and in larger doses to vasoconstrict all regional circulations except the coronary and hence to increase cardiac work and decrease cardiac index. 2. may cause shock. 3. may lead to reversal of the Starling mech anism (which causes net movement of fluid into the circulation in shock) and thus cause haemoconcentration. 4. do not alter the mortality in shocked dogs from the control value in untreated dogs. 5. have not affected the mortality from cardiogenic shock in man which remains at 80%. The value of these drugs is limited solely to the inotropic effect observed with small doses which is probably useful in a few cases. α-BLO CKIN G DRUGS α -blocking drugs such as phenoxybenzamine or chlorpromazine can be used to provide a low pressure/high flow system which is prob ably more useful in preventing tissue hypoxia than the high pressure/low flow system achieved with noradrenaline. T h e logic of α is that vasoconstriction will be re duced, resistance will fall, capacitance will rise and the reduction in pressure will mean less pressure work for, and a lower oxygen con sumption by, the heart. The fall in resistance will lead to increased cardiac emptying and the increased capacitance may be useful in the treatment of pulmonary oedema.
Infusion of fluid-plasma, L.M .W .D ., blood -is often combined successfully with this therapy but central venous pressure must be monitored to warn of impending pulmonary oedema. Th e following facts are known:-1. W ork on " shocked dogs" shows that phenoxybenzamine plus intravenous fluid leads to a very significant increased sur vival from cardiogenic shock as compared with control or noradrenaline treated animals. 2. In general, survival is improved when the pressure work of the heart is decreased and the volume work is increased -how ever, the use of intravenous fluids alone, as recommended by Nixon, is not a de sirable procedure since the damaged heart is unlikely, in most cases, to operate on the ascending portion of its starting curve in response to distension. 3. α -b lo c k in g drugs have been useful in the treatment of low output surgical shock.

LOW MOLECULAR WEIGHT DEXTRAN (L.M.W .D.)
L .M .W .D . decreases blood viscosity, in creases circulating blood volume, activates fibrinolysis and is valuable in the treatment of disseminated intravascular coagulation or sludging. In shocked dogs it improves pros pects of survival.

HYPOTHERMIA
Reduction of body temperature to 3 3°C re duces oxygen consumption to ⅔ normal and therefore decreases the demand for oxygen in the tissues. The technique has been used successfully in septic but not in cardiogenic shock. It may be that the enhanced myo cardial efficiency is not enough to compensate for the increased risk of arrhythmias.

DIGITALIS
Digitalis should be used in cardiogenic shock where the improved myocardial effic iency which results probably outweighs the increased risk of arrhythmias.

STEROIDS
Massive doses of glucocorticoids (30 mg./kg. prednisolone, 150 mg./kg. hydrocortisone) are in vogue for the treatment of low output sur gical shock in man and experimental cardio genic shock in dogs. Such large doses cause vasodilatation and may help to maintain the integrity of cell membranes and sub-cellular particles such as lysosomes. T he use of such large doses in cardiogenic shock is not record ed; smaller doses are ineffective.

ASSISTED CIRCULATION
Most cases of cardiogenic shock are going to die in spite of the administration of oxygen, drugs, etc. Such eases could be helped by some form of assisted circulation. The follow ing are the most likely to be developed.
1. Counterpulsation -blood is withdrawn from the femoral artery during systole and pumped back during diastole. Th e tech nique is successful in dogs and the minor surgery required has allowed it to be tried in refractory cases of cardiogenic shock in man. Surgery can be avoided if the vas cular tree of the lower limbs is used as the pump and subjected to appropriately phased pressure variations. 2. im plantable Prosthesis -the in-series, air-powered, prosthetic auxiliary ventricles of Soroff and Kantrowitz function well but require modification in view of the high frequency of clotting and embolism from the prosthesis. 3. Artificial Intracorporeal Hearts -Twentysix have been reported since 1958 and as yet no animal has survived more than thirty hours with a functioning artificial heart. However, W .H .O. gaily prophesies cardiac factories for the future. 4. Cardiac Transplantation -Homograft transplantation is complicated by the difficulties of tissue typing, graft vs. host reaction, catecholamine hypersensitivity, homograft rejection phenomena and its detection and control with immuno suppressive therapy, but is possible. W hether the development of a successful artificial heart will precede the break through in the problems of cardiac trans plantation remains to be seen. M ean while, there is adequate time to consider the implications of either.

SUM M ARY
An attempt has been made to present an up-to-date account of the pathogenesis and therapy of cardiogenic shock and to pursue as far as possible, the relationship between them. et al. (1966). A n n . R ev. M ed.,17,483 Brit. M ed. ]., 2, 481 (1966). " C ardiac Surgery", ed. N orm an London, B utterw orth (   In on e in stan ce th ey used as a co n d u it a pair o f ivory c an n u lae con n ected b y a p ie ce o f in testin e w h ich th ey had p revio u sly rem oved from a eat, and on o th e r occasions they used sim p le m e ta llic tubes.
T h e results o f their w ork are care fu lly d o cu m en ted an d , sin ce th ey p rec ed ed P aste u r's d iscoveries by seventy-five years, and those o f L a n d ste in e r on b lood groups b y on e hun dred and fifteen years, the e xp erim en ters m ay be excused fo r m arv e llin g th at the recip ien t an im als alm o st in variab ly took a v io le n t rigor and exp ired sh ortly after the tran sfu sion , and for co n clu d in g that b lood tran sfusion w as not a practical pro ced u re.
In the en su in g years n u m erous advances w ere m ad e w h ich m arked the d e ve lo p m e n t o f tran sp lan tation surgery as w e kn ow it today. T h ro u g h o u t this period tech n ical ab ility has u su ally been m ore advan ced than u n d erstan d A lth o u g h H u m p h re y D a v e y described the n arco tic p ro perties o f nitrou s o xid e in 17 9 8 , and suggested its p ossib le use in surgery, alm o st h alf a ce n tu ry w as to elapse b efo re anaesthesia was ap p lie d , first in den tistry by W e lls and M o rto n in the States, and later in surgery and m id w ife ry b y L isto n and Sim pson in B ritain .
T h e se discoveries tran sform ed surgery from the art o f the ligh tn in g craftsm an in to a m ore leisu rely exercise w h ich w ould allow the m ore tim e-con su m in g and exactin g w ork required for tran splan tation .
A n y tissue th at is severed from its blood su p p ly in order to b e placed in a new situation passes through a period o f su scep tib ility to in fe ctio n , a co m p licatio n that was the fear o f n in eteen th cen tu ry surgeons. T h e discovery o f m icrobes in the 18 6 0 's led first to the eradication o f in fectio n b y an tisep tics and later to the n otion that it was b ette r to avoid it b y the asep tic m eth od that is a corner stone o f m odern surgical technique. T h e im p o rt an ce o f these events to tran splantation surgery can n ot be over em phasised , b u t w ith o u t the m ore recent discoveries o f su lp h on am id es and an tib io tic substances in the 19 3 0 's and later, the advances that w ere to fo llow the e lu cid ation o f the im m u n ological rejection of trans plants from one in d ivid u al to an oth er could n ot have taken place.
In the first tw o decades o f the tw entieth cen tu ry there w as m u ch d eb ate con cern in g the failu re o f allografts o f tu m ou r and norm al tissues to survive. T h e re is n o t space h ere to discuss all the theories that w ere advanced, b u t am o n g them was the n otion that th e h ost d eveloped an active im m u n ity to the graft. Several clin ical instances w ere reported o f the b eh aviou r o f skin allografts used in burns and in extensive traum a du rin g this period, b u t u n derstan din g that a failed allograft was fu n d am e n tally d ifferen t from a failed au to g raft was slow to develop. In 19 4 3 G ib so n and M e d e w a r 4 reported the accelerated rejection o f a second set of allografts from the sam e d onor to the sam e recipien t in a case o f burns, and this led on to M e d e w a r's system atic study o f allografts pub lished in 19 4 4 and 19 4 5 .5 " H e established that in rabbits, such grafts w ere in variab ly rejected w ith a m ean survival tim e o f 10 .4 days, and that if a second g raft was m ade from the sam e d onor to the sam e re cip ie n t tw elve or m ore days a fte r the first, re jection was acco m p lish ed m ore rapidly, w ith a m ean survival tim e o f 6.0 days.
H e also fo u n d that w hereas first set grafts developed vascular con n ection s and b ecam e infiltrated w ith m on on u clear cells prior to rejection, second set grafts o f skin failed to b ecom e vascularised at all; th ey rapidly b ecam e n ec rotic, and such m on on u clear cells as w ere seen w ere heavily am assed in the recip ien t tissue w h ich was the g raft bed. A ffe re n t an tigen ic m aterial gains con tact w ith the lym p h atic tissues o f the h ost via the b loodstream , b u t in p articu lar w ith the regional lym p h nodes w hich receive lym p h d irectly from the graft. L y m p h o c yte s in the paracortical areas o f the lym p h nodes respond to the an tigen ic stim u lu s b rou gh t to them by m acrop h ages retu rn ing from the g raft b y trans fo rm in g into a new , and now h ig h ly special ised group o f cells, w h ich arc able to pro duce specific an tib o d y to the antigens con cerned. T h is ch an ge is in som e w ay im p rin ted o n the g e n e tic m echanism s o f the nu cleus, so that the pro geny o f such tran sform ed cells w ill possess this specific p o ten tiality. T h e se events m ay be called the central response.
T h e se specialised cells m ay b eh ave in two w ays. S o m e, rem aining in situ, p ro d u ce spec ific an tib o d y w hich passes in to the circu lation . O th ers, m ig ratin g from their lym p h node origins, en ter the blood stream and are able to pen etrate the g raft w here, by m echanism s un kn o w n , they exert a h arm fu l effect on the graft.
Su ch is the effector m echanism of tran splantation im m u n ity.
It should b e em phasised that a very great deal rem ains to be clarified ab o u t these im m u n e responses, in particu lar w ith regard to the role and in ter relationships o f the cells in volved; th e fore go in g is no m ore than a b rie f ou tlin e o f pre valen t theory.

METHODS OF IMMUNOSUPPRESSION
T h e fu n d a m e n ta l p ro b lem to be overcom e in the case o f allo grafts is s im p ly stated ; the a b ility o f the h o s t's im m u n o lo g ical m e ch an ism s to d estroy the g raft m u st b e suppressed w ith o u t a t th e sam e tim e sup p ressin g h is im m u n ity to o th e r fo reign m aterial, e.g. b acteria, viruses and fu n gi. T h e reader w ill be q u ick to p o in t o u t that these difficu lties h ave n o t pre v en ted th e su ccessfu l tran sp lan tatio n o f co r neas ob tain ed from cadavers. T h e reason for this is th at sin ce cornea is an acellu lar and avascu lar stru ctu re, it is n o t su b je c t to th e cell m ed iated im m u n e response m o u n te d b y the re cip ien t.
A n y process le a d in g to vascularisation o f the g ra ft results in its rapid rejection.
E in som e species, e.g. rab b its, guinea pigs andm ice, co rtiso n e pro lon gs the survival o f skin grafts, in others, e.g. dogs, m on k eys and humans, it is ineffective when given alone. As an adjunctive treatm ent to azathioprine, pred nisone has com e to play an im portant part in clinical im m unosuppression. Large doses of prednisone, e.g. 2-4 mg. per kilogram, are effective in reversing acute rejection pheno m ena, and in fact, in the case of renal trans plants, m any patients becom e dependent on a dose of 0 .2 5 -0 .5 mg. per kilogram.

Actinomycin
A ctinom ycin C is a m ixture of a group of antibiotic substances derived from Streptomyccs chrysom allus which has a cytotoxic effect. T h is appears to take the form of an interference in the control which desoxyribo nucleic acid exerts over messenger ribo-nucleic acid. It is m ost useful in the treatm ent of rejection crisis, when it is given as a short course of one or two intravenous injections in conjunction with increased doses o f pred nisone and m axim al doses of azathioprine.

Antilym phocytic globulin
T h e above agents, by their nature, have an effect on all the cells and tissues of the body, and therefore produce various unwanted side effects.
T h e antim etabolite and cytotoxic drugs m ay be responsible for agranulocytosis, throm bocytopaenia, ulceration of the alim en tary m ucosa, and loss o f hair.
Prolonged treatment with steroids produces the typical Cushingoid facies, with triae, moon face, osteoporosis, and increased incidence of hyper tension and peptic ulceration.
It has long been hoped that a m ore specific agent m ight be produced which would inhibit the m ech anisms prim arily responsible for transplant im m unity w ithout at the same time interfer ing with resistance to bacterial infection, or dam aging other im portant groups of cells, e.g. the epithelial cells of the alim entary tract. T o som e extent, these hopes are fulfilled b y anti lym phocytic serum, which has recently been the subject o f intense study in m any laboratories throughout the world, and has been used in a num ber o f cases of renal transplantation. T h e concept of an antilym phocytic serum is not new, and such a serum was prepared as early as 19 3 7 by C h ew and Law rence, who dem onstrated its ability to suppress the peri pheral blood lym phocyte count in vivo. Sim ilar suppression was obtained by W o odruff, W o o d ruff and Form an in 19 50 8 when it was noted that the lym phopenia was relatively short lived; because o f this, it was at that time thought that antilym phocytic serum would be unlikely to have a significant influence on allograft survival.
Sligh t prolongation of skin graft survival was shown in 19 6 1 by W aksm an, A rbouys and Arnason,7 but later observations in Edinburgh by W o od ru ff and Anderson, in 19 6 3 and 1964,9 dem onstrated that skin graft survival in rats could be significantly prolonged by the adm in istration o f a scrum raised in horses against rat lym phocytes. It was then shown that pro longed lym phopenia was not a necessary pre requisite for graft survival. In the past four years, extensive research into the production and properties o f these sera has been carried out, and highly significant contributions have been m ade in our own m edical school.
A ntilym phocytic serum is m ade by injecting a preparation of the lym phocytes of the species in which grafting is to be carried out into another species. U sually the serum is raised in a large anim al for transplant experim ents in a smaller anim al, for exam ple, horse anti dog serum, rabbit anti-mouse serum, and so on . It is possible to prepare cell suspensions rich in lym phocytes from spleen, thymus, lym ph nodes, thoracic duct lym ph, or peri pheral blood. A fter a course o f active im m un isation by these cells, the anim al is bled and the scrum so obtained is heated to 5 6°C to destroy com plem ent.
A t this stage dangerous anti-erythrocyte activity is present, irrespective of the origin of the innoculated lym phocyte suspensions; the scrum also contains large am ounts of un wanted protein which m ust be removed. Purification may be carried out by several techniques, but our m ethod has been to carry out sodium sulphate precipitation and batch chrom atography on diethylam inoethyl cellu lose, restoring the salt concentration to physio logical levels by dialysis prior to storage at -2 0°C .
T h e final preparation consists of im m unoglobulin G , or Ig G for short. It is absorbed against red c ell strom a and platelets in order to reduce its activity against these elem ents in treated animals.
A nim al experiments have shown that anti lym phocytic globulin (A L G ) possesses power ful im m unological properties. F o r instance, it has been shown to suppress the production of humoral antibodies to prim ary im m unisation by num erous antigens; it can inhibit cutaneous phenomena which are due to the cellular re-spon se of delayed hypersensitivity, for example, the tuberculin reaction; it can prolong the survival of allografts of skin, kidney and other tissues, and it can m odify the course of certain auto-immune diseases, 'for example allergic encephalomyelitis in mice.
Evidence is now available, notably from Starzl in Denver, 110 that A L G , used in con junction w ith reduced doses of azathioprine and prednisone, gives results in h u m an renal transplantation that are at least as good as, and probably better than, those obtained w ith these agents administered together in their usual dosage.
Since both azathioprine and prednisone have potentially serious side effects, this observation is highly significant.
H o w ever, this powerful new tool is not w ithou t its problems; its antiplatelet activity is sometimes troublesome, and the injection is often pain ful. A ltho ugh it is able to suppress hum oral and cellular im m u n ity , it is itself a foreign protein, and in fact it has been shown to be if anything more antigenic than norm al gamma globulin derived from the same source. T he reason for this probably lies in the fact that it homes onto lym phocytes w hich, being altered in some way, are taken up by macro phages resulting in the absorbed A L G being concentrated in the very centre of the treated an im al's im m u n e defence m echanism .
T he m ode of action of an tily m pho cytic globulin is only partly understood. There is no do u b t that the active molecules in an A L G preparation adhere to lymphocytes, b u t what they do in this situation is less certain. Three m ain theories have been advanced; that the lymphocytes are destroyed by A L G ; that their cell m em brane is so occupied by A L G m ole cules that it is unable to respond in the norm al way to other antigens (blind-folding); and that lymphocytes are transformed into a type of cell which is im m unologically inactive (sterile in activation). Space w ill n o t allow a discussion of these and other theories, and the experi m ental evidence which supports or refutes them , for w hich the reader is referred to spec ific works on the subject.1 TISSUE TYPING These then arc the ways at present available to overcome the hom ograft reaction. A t best they arc imperfect tools, and therefore the problems involved in avoiding or m inim ising rejection achieve the greater im portance. The laws governing the transfusion of blood which concern the A B O grouping system m ust not be transgressed. Rhesus antigens are of m uch less im portance, as are the numerous antigens which have been identified on the red cell m em brane. In recent years attention has been turned to antigenic determ inants w hich arc present in the leucocytes of peripheral blood. Pioneers in this field have been Terasaki in Los Angeles, Dausset, V a n R o o d and C epellini in Europe, and Batchelor in L on do n. They have collected sera from patients who have been sensitised to foreign leucocytes, for ex am ple from pregnant w om en, or from people w ho have received m u ltip le blood transfusions. T he antibody content of these sera has been characterised and it is possible by their use to define w hich antigens are present on a given patient's cells, and to correlate the degree of com patibility between recipient and donor with the clinical course of a transplant. E valu ation of leucocyte typing continues, b u t it would appear already that there is in m any (but not all) eases a correlation between high donor-host com patibility and sm ooth clinical course, free from rejection episodes.
T hat some cases of com plete com patibility never theless develop a rejection crisis may be taken as evidence that there arc other parameters of com patibility testing of which we are n o t as yet aware. A m o ng them may be preformed hum oral antibodies, particularly in the case of kidney recipients w ho m ay have been trans fused w ith scores of bottles of blood during their period of rehabilitation on dialysis prior to transplantation. A lthough the im portance of such antibodies has been d o u bte d' it may be necessary to revise this view when sufficient inform ation becom es available.

BACTERIOLOGICAL PROBLEMS
T he m anagem ent of patients on im m u n o suppressive treatm ent presents certain prob lems, especially in the case of renal transplants where general resistance to infection is d im inished and the rate of excretion of drugs uncertain. T he effects of a change in dosage of azathioprine arc not seen for a few days, and it is sometimes very difficult, dem anding considerable experience, to negotiate the nar row way between too little suppression, w ith the dangers of rejection, and too m uch, with the equally unwelcom e dangers of infection. It is because of this problem that it is preferred to manage these patients in a sterile area such as has been constructed at the Nuffield Trans-p lan tatio n U n it in E d in b u rg h , w h ere all pos sib le precau tion s such as the design o f the un it, an elab orate ven tilatio n system , bacterial surveys and d eco n tam in atio n o f n u rsin g and m edical staff, h ave been taken to m in im ise the colon isatio n o f the p atien t b y organism s o th e r than his ow n.
A R T IF IC IA L AIDS TO VISCERAL FUNCTION A p atien t w h o is in th e term in al stages o f disease o f one of h is visceral organs, b e it k id ney, liver, lu n g or heart, such that his only 'hope is tran splan tation o f a n ew organ, is usu ally in a desperate clin ical state. L o o k in g back at the early days o f renal tran splantation , there is no d o u b t that a great deal o f the peri-operative m o rtality, and the early failures, w ere due to the fact that the recipien ts w ere often m o rib u n d , h avin g been saved from death itself b y on e or tw o hair-raising h a em odialyses. T h e d evelo p m en ts in dialysis tech n olo gy in the early 19 6 0 's, lead in g to the in trod u ctio n b y Scrib n er o f lo n g term in te rm itte n t dialysis for ch ro n ic renal failure, tran sform ed the situ ation in tw o w ays. F irstly , an altern ative to tran sp lan tation b ecam e availab le in w h at has b eco m e know n as repeated dialysis treat m en t or, b y that h ab it o f ab breviation to w h ich m edical m en are so ad d icted , as " R .D .T ." Se co n d ly, repeated dialysis treatm en t allow s a p atien t w ith term in al renal failu re to b e re h a b ilitate d so th at h is p h ysical con d ition is no lon g er a bar to the relatively m ajor operation o f tran splantation w ith its atte n d an t hazards relatin g to im m u n osu ppression .
Su ch co m p lication s as h yp erten sion , oedem a, ascites, con gestive heart failu re and in fectio n s can u su ally be e lim in ated or con trolled du rin g this period, lead in g to a g reatly im proved chance o f su rvivin g the operation. H avin g ob tained an organ fo r tran splant atio n , tim e is vital, and the co m p le x logistic pro blem s in volved in m o b ilisin g the surgical team , the recipien t, and such an cillary services as fo r exam ple, blood tran sfusion, blood coag ulation and clin ical ch em istry w ould be m uch sim p ler if the organ cou ld be stored in a viable state fo r a n u m b e r o f hours or even days. C e r tain advances have been m ade alo n g these lines in the ease o f the k id n ey, and, m ore recen tly, the liver, using h yp o th e rm ic p erfusion w ith electro lyte solutions, b lood , lo w m o lecu lar w eigh t dextran , m an n ito l, or co m b in atio n s o f these m aterials, in co n ju n ctio n w ith h yp er b aric oxygen and, w hen tem peratures b elow Posto p eratively she was slow to recover con scious ness and sudden ly d eteriorated 1 8 hours later. R e-exploration show ed an accu m u lation o f clot from recurrent venous oozing. Sh e rem ained deeply un con scious and som e 24 hours later d eveloped an intense ja u n d ic e : urob ilin ogen and b iliru bin appeared in th e urine. P ro th rom b in activity w as 2 9 % , S .G .P .T . 570 I.U ., serum in d irect b iliru bin 2 .5 m g / 10 0 m l, direct 5.7 m g / 10 0 m l. B le ed in g tim e was 9 m in u tes : no increase in fibrin degradation products : direct and in direct co o m b s' tests n e g a t iv e : sligh t depression o f vitam in K -dep en d en t coagu lation factors (II, V I I and X ). In spite of treatm ent in clu d in g triple strength plasm a and vitam in K 1 h er con d ition deteriorated and she died 6 days after operation. C . W h a t w as the cause of her jaundice?

DIGITAL EXAMINATION
T h e use o f the ob server's eyes and forefinger w ith the in itial ch an t of, " N o w ju st turn over on you r le ft side facin g aw ay from m e and draw you r knees u p " , so realistically caricatured by O 'G ra d y (19 6 3 ) is the first step in the " rectal" .
W h a te v e r the selected p atien t p o sitio n , en sure that you have a good lig h t o n the peri anal area and pro vid e an in te rm itte n t co m m en tary fo r the p a tie n t's b en efit. P art the b u ttocks and m ake a thorough visual exam in ation of the anal area fo r evid en ce o f traum a, sore patches o f skin , lich e n ificatio n , ulcers, thread w orm s, blood or m ucous, " p iles" and skin tags, fissures and fistulae, p ilon id al sinus, the h ig h ly con tagiou s syp h ilitic con dylom ata (warts) or o th er signs o f anal sexual con tact, or a pro lapse o f piles, anal canal or uterus, and note w h eth er the anus is w ith draw n or patulous.
T h e re are two m eth od s advocated for in sertin g the finger as pleasan tly as possib lecovered in a so ft fine ru bb er finger stall or sim ilar tw o or five-fingered glove. T h e better m eth od is to ask the p atien t to bear dow n, i.e. to increase his in tra-abdom in al pressure and thus cause a m ild protrusion of his anal ring. A s he does so, ge n tly ap p ly your exam in in g forefinger w ith the lo n g axis o f its cross section in lin e w ith his an terior ( 12 o 'clock) -posterior (6 o 'clock) anal p lan e and allow your finger to be ge n tly sucked inw ard as he releases his intra-abdom in al pressure. T h e re su lt is that you r finger w ill find itse lf in the rectum alm ost un bekn ow n to the patien t.
T h e second m ethod is to place the p u lp of the distal ph alan x o f your e xam in in g forefinger flat against the anal ring and then grad u ally to pass it inw ards, w h ile at the sam e tim e slow ly sw in gin g the finger through a 9 0° angle un til the tip p oin ts throu gh th e anal canal. W h ic h e v e r m eth o d you choose, n ever stab you r finger at the anal o p en in g because the suddenn ess w ill surprise you r p atien t and the m in or in evitab le pain w ill p ro d u ce yo u r n u m ber one en em y -spasm .
Y o u m u st n ow assess and m ake a decision u p on :-

1) T h e an al sp h in cter
T h e in tegrity of this m uscle m echanism is essential to m an 's w ell-being, for as D r. I f you suspect an em otion al cause, pause and in dulge in fu rth e r con versation and explain your trouble to you r p atien t and ask him to assist you b y con ce n tratin g on a regular deep form o f b re ath in g and to relax as m uch as he can.
F a ilu re to ach ieve a reasonable relaxation o f the sp h in cter at this stage m ay virtu ally n u llify an y fu r ther m anoeu vres.
A lax and toneless sp h in c ter often associated w ith a patulou s anus is an un usual con d ition and a cause such as rectal prolapse w ill usu ally be eviden t.

2) T he A nal R in g
W h en all is settled, palpate the entire perianal ring between the pulps of the external thum b and internal forefinger, noting any lum ps, cysts, foreign bodies, loculated pus, irregularities, pain-spots. etc. T h is practice is im portant and often passed over in the hurry to assess the rectum.

3) T h e Tem perature of the Rectum
T h is is a very good indication of gen eral body temperature. T h e A ncients, we are told, could detect early typhoid from a hyperpyrexic rectum.

4) The Size of the R ectal Cavity
T h e space in which your finger finds itself is very inform ative.
It may be grossly ballooned as with a m egacolon or from a longstanding condition of im pact ed faeces, it m ay represent the contracted rectum of longstanding ulcerative colitis, or the normal state in which the rectal walls are within easy reach of your finger tip.

5) Faeces
Som e 50% of the time the rectum is em pty, but if there are faeces present, de cide whether they are hard (scybala), indentable, soft, or fluid and try to make your findings fit the facts. For Exam ple: A rectum full of hard, "im p acted " faeces is liable to occur in the elderly, those clinically confined to bed, patients in the tropics, those who drink insufficient fluids, and those very ill or with high temperatures. Such ob structions m ust be m anually removed before you can hope to achieve maximal information from your exam ination. A proctoscope is often useful for this pur pose.

6) T h e R e cta l M ucosa
T h e condition of the rectal mucosa is very informative. T h e normal state has a characteristic feel and should be mobile. If it is bound down at any point, such as over the prostate, suspect active disease (cancer) or the fibrotic aftermath of pre vious affliction (gonococcal).

7) Suspicious Lesions D e ep to the R ectal
W a ll I f you have been using the lateral pos ition, rotate the patient into the supine position, keeping your exam ining finger in situ and proceed with a further manoeuvre. Bim anual palpation, by applying pressure with your remaining free hand firmly and gradually in the suprapubic region while you ask the patient to bear down and relax his abdom inal wall in gentle suc cession, will force the lower abdom inal and pelvic contents towards your exam ining forefinger and will remove m any lesions from your diagnostic list o f possi bilities.
Individually palpate the four points of the internal rectal compass while the patient strains down, questioning at each cardinal site as to the presence of increased discom fort, tenderness and pain.
T h e norm al fallopian tubes, seminal vesicles and often the ovaries w ill not be palpable, but the bim anual technique w ill allow you to assess the characteristics of any suspicious lum p in terms of site, size, shape, surface, consistency, edge, the fascial level in which it lies, any associated pain, any related loss of function or presence of abnormal lym ph glands draining the area -after Sir Jam es Paterson Ross (Ex P .R .C .S .).
Y o u r examination concluded, withdraw your finger, wipe your gloved finger on a piece of filter paper or keep the glove itself with its small surface com plem ent of faeces and intrarectal contents for brief m acroscopic exam in ation and sim ple tests such as hem atest, for occult blood.
Explain to the patient that you arc finished and com plim ent him on his co-operation. Thoroughly tidy the patient's anal area, apply a pleasant cheap powder (Johnson's Baby Powder) from a plastic blower bottle and cover his exposed hindparts w ith a concealing sheet. T h ere is nothing m ore unpleasant to a patient than of knowing the anal area to be covered in jelly, of having experienced the sensation of having passed a m otion, or not being properly tidied up and of having his posterior " to human view displayed" .

THE SIGMOIDOSCOPE
Should the previous proceedings detect any thing that worried you, proceed im m ediately with a sigmoidoscopy.
T h is instrum ent need not be above 25 cm. in length for the normal adult (a smaller one for children), to visualize the hem orrhoidal area (10 cms.), superior hem orrhoidal area (10 -15 cm -), the recto-sigmoid junction (15-18 cm.) and beyond into the early sigmoid colon.
In this day and age the instrum ent should be equipped w ith an independent battery sup ply in the pistol-grip handle or with a re chargeable m iniature power supply, sim ilarly sited.
T h e era of leads connected to dry batteries is past.
T h ere are three m ethods of bringing light to bear on the distant subject. L igh t can be provided from a small bulb proxim ally (Lloyd-Davies m odel -good) or distally situated (Strauss model -not so good) w ithin the tube of the instrum ent. Illum ination can also be provided by use of the principle of inter nally reflecting light down the instrum ent's cylindrical walls of transparent plastic from a powerful light-source in the handle.
T h e latest developm ent is that of the excel lent disposable sigmoidoscope.
Such equipm ent contrasts very favourably with the cold m etallic monstrosities that are equipped with a flickering light emanating from a loosely fitting bulb, supplied by an ancient battery through a temperamental rheostat that invariably " blows" the bulb at the crucial m om ent.
T h e instrum ent is laid-up on a trolley equipped with supporting proctoscope, swab-holding forceps, or better still, swabs on long sticks, biopsy forceps, a bowl of swabs some of which arc subm erged in a second bowl of body tem perature 1/ 2 0 0 C h lorhexidine in saline solution, a powder squirter, and a pot of lubricating jelly.
T h e " jelly" should be water-soluble and supplied in a wide-mouthed pot so that the instrum ent or finger can be lubricated evenly in one fell m ovem ent. T u bes of jelly such as " L u b afax" and " K Y " are fiddly, expensive and are not satisfactory, while yellow paraffin or vaseline should be forbidden. V aseline is thick and stiff at room temperatures which makes an even application to the forefinger difficult, reduces the sensi tivity of your probing finger, is useless for in strum ent lubrication and can be sensed in the anal area by the patient for m any hours after the exam ination is finished. T h e follow ing recipe is for a cheap and effective form of lubricating jelly.   It is far b ette r to be satisfied w ith an 18 cm . traverse and see w hat you can discover w ith the aid of the radio logist b eyon d this p o in t, p u ttin g the distan ce you actu ally ach ieved un der observation on your x-ray request form alon g w ith th e oth er relevan t clin ical in fo rm atio n . I f du rin g this process you w ish to take a biop sy there are a fe w practical poin ts to co n sider; b u t do n o t p erform the b io p sy you rself unless you kn ow w h at you are doing.
Y o u m ay perforate the b ow el w all w hen sam plin g above the recto-sigm oid ju n ction or you m ay not b ite d eep enou gh and m iss th e all im p o rt an t b asem en t m em brane.
I f the o b je ct is sm all, e.g. a p o lyp , it is w orth rem ovin g the w h o le specim en .
If, h ow ever, the lesion is a large ulcerated g ro w th , the path o lo gist gen erally appreciates a fu ll d escrip tion w ith a sn ip p et from the cen tre an d one from the margin as the centre may just dis close necrotic matter.
W hen you have procured the specimen with a minimum of trauma do not wipe it off the biopsy instrument with a piece of gauze and view it with a hunter's pride. Such a practice can cause a rapid dehydration of the peripheral cells with a resultant loss of many useful path ological diagnostic signs.
There is no need for hurry in these pro cedures, but quick and decisive movements are optimal if the specimen is being collected for histochemical enzyme or electron microscope studies. Normally it is quite sufficient to take your time and to put the end of the biopsy forceps straight into your plastic pot of Zenker's Formalin, shake off the specimen, label the container, and carry the specimen to the laboratory yourself or make sure a reliable and informed messenger has it in his charge. The specimen must be accompanied by a note designating your requests and supplying sensibly relevant information for the pathol ogist's benefit. Finally, and before doing any thing else, describe your procedure and findings in a few well-chosen words in the patient's notes.

T H E P R O C T O S C O P E
This instrument has been left to the last be cause the indications for its use at the present time are becoming less numerous. It is accept ed now that the digital, followed by the sig moidoscope is the routine of choice. However, the proctoscope is still a very useful instrument fo r : 1) Reviewing lesions in the terminal 5 cm. of the rectum and for this a rotating grooved barrel instrument (W elch-Allyn) is a prac tical variant. 2) For the injection treatment of first and second degree " piles " using a tuberculin syringe (1 ml) and a 4" needle. 3) For the removal of excessive numbers of faecal lumps prior to a successful sigmoid oscopy.
The light for a proctoscope can also be sup plied from power supplies in the pistol grip handle but in the interests of simplicity and expense, illumination from an angle-poise lamp, suitably held torch, or conveniently placed window is usually quite adequate. For future geographic anal reference purposes it is usual to use the clock terminology -that is.
12.00 is anterior between the legs and 6.00 is posterior. The classical position for hemorr hoids is that of 4-7-11 o'clock, a figure easily remembered by those who delight in " 4711 " Eau de Cologne.
The " take home message " is that a rectal examination is mandatory whenever there i s :-1) Bleeding from the rectum or evidence of melena. 2) Protrusion of mucosa from the rectum.
3) A change in the intestinal rhythm or con tent of the motions. 4) A " p ile " (Hemorrhoid) present. 5) Pain in the lower abdomen and backache. 6) A discharge of pus or mucous P.R. 7) Pain in the ano-rectal area. However, whatever the indication -digital rectal, proctological and sigmoidoscopic exam ination is neither burdensome nor difficult and for the patient, may be life-saving.
Finally, and before you leave the patient, explain to him what you have found and see that he is once again decorously dressed and comfortable. This last refinement is most es sential because the majority of your patients will not have been so treated previously, and may mildly resent your assault -not apprec iating the vital importance to you, the doctor, of such an examination. Handle the whole situation from start to finish with decorum, good maners and employ a matter-of-fact form of grace that will spare him any form of em barrassment. If you can accomplish this suc cessfully you will find that the mental reaction within the patient will not be one of resent ment but will be one of a grudging, but friendly, "W e ll this man is at least thorough." P u lve r, K raep lin and K la g es, A llp o rt, V e rn o n an d Sau d ek , R o m a n , Le w in so n and Zubin, these are the nam es that h ave in trod u ced a com m on sen se, rh yth m ical and balanced lin e to h an d w ritin g analysis. W h ile not e n tirely accep tab le, it is in triguin g and fu ll o f prom ise. In e v ita b ly the su b ject finds itself variou sly ascribed to a booth alon g w ith M m e . L izan d ra and her m agic b all, p h ren o logists, h om eop ath s and cocktail p arty astro logers, or to the lab oratory w ith psych om etrists, fo ren sic scien tists and em ployers. It is not an en tirely h ap p y resonance.

B E Y O N D T H E T R A C E S
A n y tracker w ill be ab le to tell you a deal ab o u t p reced in g events b y ob servin g scuffs in the sand, fo o tp rin ts, sp en t m atch es and so on. H an d w ritin g is a sim ilar spoor or tracing, rep resenting the fo cused activities o f a person as th o u g h t fo llow s th o u g h t and is relayed. So m e claim , lik e th e tracker, to b e ab le to assess the reasons b eh in d th e m arks, and then b y fu rth e r stu d y to gain in sigh t in to the p erson ality and w orkings o f the w rite r's m in d . T h e y m ain tain that w ritin g style is a p ro d u ct o f p erson ality, as is an y ob servab le b eh avio u r, so lo n g as som e co n tro l can be im posed on the en viron m en tal situ atio n . T h u s traits, recognisab le in any scrip t (and d iffe re n t cu ltu ral form s pose the usual pro blem s here), tally w ith d e fin ab le traits in personality. O th ers do n o t m ake this exten ded claim w ith grap h o lo gy b u t feel it has great use in m o n ito rin g the changes in a p er so n 's character, w h eth er from experien ce, drugs or therapy. N o claim s are m ade that it allow s gre ate r in sigh t into a certain person ality than on e or tw o in terview s w ould afford , b u t its pro je ctiv e p e rm an en ce is extolled. T h e earliest form of sym bolic and permanent com m unication utilised the knotting of reeds and twine, follow ed eventually by the engrav ing of designs on wood or stone. T h ese m arkings were necessarily effected by hand. T h en came the pictorial techniques of ancient writing, the hieroglyphics of E gyp t and the ideograms of C hina, still in use today. T h e direction of flow of these pictures was variable with different cultures, or could be read across or from top to bottom as with the Cartouche of Cleopatra on the Rosetta Stone. It was not until sim plified symbols began to be strung together, like replicas of articulated sounds, that writing developed a fluency of line.
A ncient G reek and H ebrew maintain a backwards and forwards m ovem ent with suc cessive lines, rather like the plow ing of a field. T h e gradual predom inance of left to right flow has been attributed to the greater proportion of people born right handed, it being easier to write in a direction away from the body.
T h e explanation m ay be m ore com plicated however. In his studies of the right to left writing o f the Szekely tribe o f Transylvania, the Hungarian anthropologist Sebestyen ob served how one of the last adherents to this language wrote in vertical colum ns from top to bottom , but beginning at the left; then to read the message the inscription was turned in a clockwise direction till the lines were horizontal. T h e newly aligned writing was of course read from right to left, apparently against the rules of predom inant right handed ness, though the actual writing had been from left to right in columns.

SLANTS AND SLOPES
T h e slant of handw riting is one of the first features to srike the eye. A rightward slant is one that leans m ore than five degrees from the vertical in its upper zone. T h is is m eant to depict the self reliant, feeling personality and only when it becomes significantly tilted, 45 degrees or more, docs it indicate someone with an over-excitable and sentim ental tem perament. T h e alcoholic is reputed to m ani fest this excessive slant, along with unsteady, tremulous strokes of the pen and a tendency to write lines that slope downwards towards the right. H itler's nearly prone signature is likewise looked on as revealing severe path ology.
E rect writing, within 5 degrees of the vertical, indicates the person governed by reason.
It is certainly a more controlled variety of script and it is interesting that an academic training often induces a straighten ing of the script. M uch will depend on the writing school of the person when young and on his com pliance with scholastic strictures. Leftw ard sloping writing, so called backhand writing, characterises the defiant individual, and if extrem e often indicates previous child hood conflicts and unresolved tension with the parents.
Som e graphologists have sug gested that the leftward slant shows up " m other fixation" , finding the slant com m on ly in m atriarchal societies. W ritin g that varies in slope represents the individual with pro nounced am bivalence of response, varying be tween fixation and protest, love and hate. In passages of expressive writing, as in letters, emotional pieces of news are often written in a m ore pronounced slant to the right than relatively innocuous sections.

LEFTHANDERS
T h e leftward slant is in fact the more natural tendency of the left hander, and in order to com pensate for this the paper is often held skew so that the resultant hand is acceptably sloped to the right. T h a t the leftward slope is more convenient for the left hander has been shown in the eases of those who lose the right arm, like N elson, and subsequently change from right to left slope while m ain taining most of the other characteristics of their handwriting. L e ft handers also show a greater facility at writing reverse image or ''m irror" writing than right handers; further more, latent left handers writing with their right hands are far m ore able to perform mirror writing than their truly right handed fellows.
Leonardo da V in ci, equally adept with either hand, wrote a conventional right handed script for general com m unication, and mirror handwriting for his diary.

THE THREE ZONES
A nother graphological technique is the dividing up of the script into zones. T hus unizonal letters like 'a ' and 'n ' occupy only the m iddle zone, whereas bizonal letters occupy additionally the upper zone, like 't '( or the lower zone, like 'g ', and trizonal letters like 'f encroach upon the full writing space. T h e m iddle zone is considered to represent the sphere of actuality, so that when it is well dc-ve loped the w riter is con sidered to be w ell in touch w ith reality and ab le to relate w ith his p ersonal an d m aterial surrou ndin gs. T h e u pper zon e is the sp h ere o f ab straction w h ere the interests and aspirations o f the m in d and sp irit find expression. A rtists and creators show pro n oun ced excursions in to this zone, though excessive flam b oyan cy or over-extension above the norm al lim its in to w h at is term ed the " strato sp h ere" show s u p the person w ho is apt to over-in dulge his im ag in ation or to day dream .
H o w ev e r if the o th e r zones are also w ell d eveloped the h an d w ritin g m ay b e p e rfectly co m p atib le w ith the h ig h ly creative m in d . D o ttin g the ' i' and crossing the ' t ' are both fu n ctio n s w ith in this zone; w hen th e procedure is carried ou t w ell ab o ve th e p aren t stem this suggests flightiness an d fan tasy, w h ile if the ' i' dots and ' t' strokes are carried con siderab ly to the right the w riter is p ro b ab ly fu ll o f verve and even slapdash. It has also been said that crossing a ' t' is a d ecisive action w h ile d o ttin g an 'i ' is a se lf con scious m o vem en t.
T h e low er zone represents the in stinctu al drives o f se lf preservation and sex. L a rg e closed loops in the zone in d icate the sensuous per son, w h ile such features as breaks in the loops, b lotch in ess, and flow ery appendages show up the person preoccupied w ith the sexual or sensual.
W h e n the loops are reduced to sin gle vertical strokes the person is eith er cold or finds h im se lf in a position w h ere his sexual life has to b e w ell governed. In m an y ways these three b asic zones are analogous w ith the p rim ord ial m etap h ysical con cepts o f a m in d, soul an d b od y, or the psycho-analytical division o f superego, ego an d id.
Persons o f lim ited ed u cation and cu ltu re, children and the old sh o w p ro po rtio n ally en larged m id d le zones. T h o s e w ith a fac ility for w ords show longer stem s and loops, the m id d le zone often redu cing to less than the three m illim etre average. I t is fo u n d that loops elon gate at pu b erty, w h ile b efore exam s they tend to len gth e n , perhaps as p en t up em otion s and in stincts are released.
A m onoton ous regularity o f loop size in dicates a du ll tem p er am en t or over-control, w hereas m arked irreg u larity is a sign o f extrem e excitab ility and lack o f con trol. T h e arcade, h eld to represen t the grasping h an d, is th e co n n ec tiv e form o f the m ore fo r m al and a lo o f personality. M ix e d con n ective form s betoken the person w ith in term ed iate traits w h ile the sharp an gu lar co n n ective form signals the sharp in tellect given to n o n co n form ism or aggression; thus regular angles de note the theoretician b u t irregu larity show s up th e ob stin ate person ality.
A tte n tio n is also paid to the lin k in g o f letters in a w ord, som e claim in g that the m ore con nected the letters the m ore logical is th e w riter.

VALIDITY AND SIG NIFICANCE
T h e re are m an y oth er cues that have been used to assess person ality from h an d w ritin g. Pen pressure, expansiveness, fluency and speed, the size o f capital and the degree o f closure o f such letters as 'o ' have all been persuasively argued as in dicators o f certain traits.
T h e valid ity o f grap h ology is con stan tly question ed, and certain ly in con trolled trials w h ere panels o f psychiatrists have assessed the person ality o f patien ts and com pared th eir results w ith the graphologists there has been poor correlation . B u t although g rap h o lo gy b y itself m ay never fu rn ish the fu ll answ er regarding personality, n eith er w ould on e e xp ect a single clin ical sign to provid e the diagnosis o f a disease. T a k e n in co n ju n ctio n w ith in terview s, q u estion naires and b ehaviou ral observations, grap h o lo gy m ay indeed be o f h elp to some professional w orkers, and as a p ro je ctive test it is som etim es preferred to techniques like the R orsch ach ink b lo t test.
G re a te r re liab ility is afforded in eases w here a su b ject is b ein g m onitored b efore and after drugs or therapy. T h e w ritin g o f depressives is often found to expand after successful therapy, changing from a hand th at was orig inally cram ped away in to the corner of a page. Sch izo p h renics w rite w ith a tidier, reduced hand a fte r im provem en t in th eir con d itio n and it is interesting to n o te th at som e sub je cts w ho respond w ith p ron ou nce d psychical and physical sym ptom atology to h allu cin o gen ic drugs, the so-called "strong reactors", show a significant increase in scrip t size, as m easured by planim etry, during the period of drug effect. " N on reactors" show no signifi can t change in size. O th e r fields th at engage the graphologist are forensic m ed icin e and the d etection of forgery, b u t these are su b jects in them selves.

SIGNING OFF
Signatures arc very im p o rtan t and represent w hat we wish to be rem em bered by. E very one is conscious o f a signature and m any have practised th eir own for hours. Personal em bellish m en ts and su btleties o f stroke are in corporated until "im p ro v em en t" is established, o ften at the expense o f legibility. C h an ge in a signature is now here b e tte r seen than in the evolution of N ap oleo n 's signature w hich was a t first sim ply w ritten and unrem arkable, then becam e fo rcefu l, heavy and slashing a t the h eig h t of his pow er, and confused, narrowed and m an ifestin g self-covering strokes after the retreat from M oscow .
Placin g o f the signature is con ven tionally to the lower right hand section o f a page. E x trem e rightward sh ift ind icates the im p atien t person w hile leftw ard placing is taken as an ind ication o f anxiety. D e je cte d or depressed people drop the signature low down on the page, th e signatures o f suicides being often found towards th e b o tto m le ft hand corner of the page. W it h all this said, it is as w ell th at th e only w riting we have to con tend w ith is our ow n, our friend s' and our colleagues' (in cluding the " D ear D r ." brigade), and th at the only people w ho have to grapple w ith our signatures when it m atters are officials and bank managers, w ho hold th e keys to our anxiety, im p atien ce and depression anyway. N o rm al m ale type baldness docs n ot q u alify for a w ig un der the N .H .S . and a p atien t m ust suffer total alopecia to ju stify prescription. N o w om an , h ow ever, can be expected to w ait u n til h er last hair dis integrates b efore q u alify in g , and thus the C o n su ltan t D erm ato lo gist often provides a prescription b efore co m p le te baldness occurs.
A survey to discover the reasons fo r the recent increase in the n u m b er o f w igs issued, was carried ou t using the records o f the R .I .E . D erm ato lo gy D ep artm e n t. A ge, sex and cause o f a lo p ecia w ere noted for all cases in w hich w igs w ere prescribed from Jan u ary 19 6 2 to Ju ly 1968. A n increase due to increased num bers of patien ts was discounted fo r although patien ts rose in 1963-64 w h en one m ore C o n su ltan t w as ap p o in ted , the n u m b er has sin ce been con stan t.
A nalysis o f specific cause s o f alopecias b y age an d sex show ed no sign ifi can t fluctu ations fo r those due to m yxoedem a, traum a, drugs or oth er specific causes b u t senile and post-irradiational alopecias h ave show n an increase. P ost-irradiation al alopecia is m o stly the result o f T in e a cap itis therapy as a child b u t o ccasionally has fo llo w ed irradiation o f tum ours.
C lo se stu d y o f senile h air loss show ed that w h ile 5 2 % o f patien ts in 19 6 2 w ere un der 70 years, 6 3 % fell into this cate gory in 19 6 6 and 6 8 % in 1968.
A last fact to be considered is the ab ol ition o f th e £ 2 10 / -prescription charge per w ig in F e b ru ary 19 6 8 and it w ill be o f in terest to see if an y decrease in the upw ard trend fo llow s its reintroduction this year. T h e conclusion is that the m ain reasons for the increase in w ig prescription are increased freq u en cy o f diffu se alopecia in you nger w om en w ith con seq u en t increase in renewals. E a c h fraction w as in cu b ated w ith C 14 ch olesterol, the products b ein g estim ated later b y thin-layer ch ro m ato grap h y and scin tillatio n co u n tin g o f each derivative.
T h e final results, a fte r calcu latio n o f b io logical variation , ten d ed to show an increase in ch olesterol-7-alpha-hydroxylase activity in th e b est gro u p , w ith a decrease in the am o u n t o f au to xid atio n p ro ducts n o rm ally fo rm ed d u r in g in vitro in cu b atio n s. I t cou ld th erefore be ten tativ e ly co n clu d ed that in creased ch olesterol in take results in increased catab olism o f the sterol to b ile acids; this sequ en ce o f events w ould tend to con trol the net size o f the ch olesterol p ool. O n e hu n d red and seven patien ts receiving treatm en t fo r the first tim e fo r p u lm o n ary tub ercu losis w ere given P A S ( 1 2 G . daily) and ison iazid (200 m g. daily).

M. Braithwaite
T h ir ty three o f these (3 0 .8 % ) had sign ifican t elevation s o f SGOT (greater than 50 R e itm a n -F ra n k e l units) du rin g the first three w eeks o f treatm en t w hen h yp ersen sitivity is m ost lik e ly to occur.
O f these g ( < 1 0 % ) had clin ical evid en ce o f h yp e rse n sitivity b u t o n ly 5 had proven h yp e r se n sitivity to P A S .
It is, o f course, feasib le th at isoniazid was the o ffen d er in th e 4 cases w ith o u t P A S h yp ersen sitivity b u t it is com m on exp erien ce that ison iazid h yp e rse n sitivity is relatively rare and scarcely e ver occurs sin gly, i.e. it is usual to find associated h yp e rse n sitivity to the co m p an io n drug.
T h e p ro blem of ison iazid h yp ersen sitivity w as n o t stu d ied in the present series.
T h e elevated SGOT values u n related to drug h yp e rse n sitivity m ig h t b e exp lain ed b y a to xic effect on an alread y dam aged liver.  M alcolm M acnicol is an honours g r a d u a te in p h a rm a c o lo g y and is n o w in his fin a l ye a r at Edinburgh. H is interests are spread widely, both inside and outside medicine, and he has first hand experience o f medical services in both Russia and America.

Gordon Leitch graduated in honours physiology and is now in fifth year. H is article on
Cardiogenic Shock is based u p o n the prize winning essay which he subm itted to the essay com petition organized by the Scottish branch of the C h est and H eart Association.

C ure of Epilepsy
In the case accompanied by the Aura E pileptica, the fit may be prevented by com pression of the part; or when we perceive the sensation proceeding from the extrem ity of any particular nerve, dividing (if possible) that nerve in its course. Am putation is the most effectual mode of putting a stop to it. Blistering and keeping up a discharge on the part by means of Issues, has been recommended.
-from Socie ty case records, 1798. A q u estio n n aire w as put out to studen ts last S u m m e r T e rm to deter m in e w h at pro po rtio n o f m ed ical studen ts m ig h t b e attracted to jo in in g the S o ciety.
T h is show ed th at 3 0 % o f stu d en ts w ere ' regu lar' attenders at extracu rricu lar lectu res, societies, sym posia, etc., i.e. atte n d e d m ore than tw ice per term ; 3 0 % did n o t atten d an y such m eetin gs, the rem ain d er (4 0 % ) b ein g 'occa sion al' attenders.
C o m p ariso n show ed that tw ice as m an y studen ts atte n d e d E d in b u rg h M e d ical G ro u p m eetin g s as R .M .S . m eetin gs; w h y this should be w e could n o t d efin itely ascertain, b u t it is sign ifican t that 7 2 % of m edical studen ts fe lt that they w ere in suffic ie n tly in form ed ab o u t R .M .S . activities.
In atte m p tin g to d efin e th e reasons fo r the S o c ie ty 's sm all m em b e rsh ip over the years, an o p p o rtu n ity was p ro vid ed for studen ts to vo ice their criticism s of the S o c ie ty 's affairs, and in d icate w h y th ey had not join ed : (a) 55% o f studen ts suggested that F rid a y n igh t was u n su itab le fo r m eetin gs, for various reasons; W e d n e sd a y stood out from o th er w eekdays as the m ost su itable altern ative.
(b) 4 0 % in dicated that th ey h ad n ever been approach ed w ith regard to jo in in g ; in d eed , a surprising n u m b e r did n o t know o f the exist ence o f the So ciety! (c) 3 3 % suggested that the 2 gu inea sub scription was p ro h ib itiv e ; this was a p articu lar criticism o f the 2nd-4th years. (f) 2 7 % th ou ght th e S o c ie ty 's business too sim ilar to the m edical school cu rricu lu m .
F in a lly , 4 2 % of studen ts said that they w ould join the R .M .S . if changes w ere m ade alon g the lin es suggested; 1 1 % said th ey w ould not jo in , the rem ainder b ein g un d ecid ed .
In view o f the ab ove figures, b u t b earin g in m in d the h isto ry and essential trad itio n s o f the S o cie ty , it seem s reasonable th at the S o c ie ty 's m em b e rsh ip could be at least d ou bled (to 2 0 % o f the m ed ical school) if p u b lic re lation s w ere im proved and som e m eetin gs held on W e d n e sd a y s; and w ith b etter p u b licity and m ore im ag in ative topics, larger audiences could be assured at P u b lic m eetin gs.
A ctio n is b ein g taken on these lin es, and there are alread y very pro m isin g signs o f sub stantial im p ro ve m e n t in m em b e rsh ip and atten d an ces.
M ain tain in g a neutral attitu d e to Professor C h ristia n B arn ard is beset w ith the sam e difficu lties as w atch in g a R a n g e rs-C eltic m atch w ith o u t taking sides. P rofessor B a rnard's address to th e S o cie ty, w h ich filled th e G e o rg e Sq u are lectu re th eatre to cap acity, was a v ic tory fo r his supporters, and I suspect w on over a fe w o f his critics as w ell. H is tech n iq u e is not so m uch one o f in itially b reakin g th e ice w ith his au d ien ce, as o f cau sin g co m p le te liq u e factio n , using his charm as a catalyst and poetry and an ecd o te as his stage-props.
A fte r a justification o f h eart tran sp lan tation , w ith an adm ission that the first operation was so m eth in g o f a step into the u n kn ow n , as all m ed ical advances are to a greater or lesser de gree, the real m eat o f the talk fo llo w ed . H ere w e w ere told ab o u t the tech n iq u es em ployed in replacing the recipient's heart muscle with that of the donor and the methods used for m aintaining the circulation during this m an oeuvre. Professor Barnard then discussed the rejection phenom ena, the way in which this had been combated with a com bination of Azathioprine, prednisone and A .L .G . and the extensive search that the South African team had made for a reliable indication that rejec tion was taking place.
A few photographs of recipients and of the hospital at C ap e T ow n followed b y one last poem, revived the men from G ram pian, who had seemed a little bemused by all the tech nical jargon and saw Barnard bowing out to rapturous applause.
A nd if one questioner did have the audacity to suggest that the Professor's experiments in heart transplantation with dogs had not m et with 10 0 % success, the audience were in no mood to swallow their angostura after the feast.
Starting the 232nd. session with the chains of tradition falling from all parts of its body, the Society can be excused if at its first m eet ing it acted a little like a cat with two tails. T h e lady presidents were showered with bou quets and professor Perry, by com bining his Inaugural Address with his dissertation to the Society earned him self a tankard of beer. T h e owner of the femur, which is still punished twice nightly under the hand of the Senior President, would no doubt be proud that the bone which served him (or was it her) for so long, is still in use. Perhaps the person who pinched the silver gavel will, even yet, one day return it.
Professor Perry in his address on " Trends in M edical Education" , placed him self more in the camp of the radicals than the conservatives in this field, although he recognised the nec essity for compromise. His lucid explanation ,, D in n e r Com m ittee -of the rationale behind the way in which the present Edinburgh medical course was con structed makes it easier for the student to accept those aspects of it which at first sight appear incongruous. T h e compromise in this case, it was explained, is a resolution of the need to provide the scientifically trained pro fessional man and the imm ediate doctor. Perhaps the first of us through the mill will be more tolerant of teething troubles and Profes sor Perry's admission that the ideal has not yet been fully achieved, helps us to realise that much thought is still being given to the problem. Let us hope that from his new job with the University of the Air, he will find time to return to Edinburgh. H e will certainly not be soon forgotten. M em ber's Dissertations will be announced during the term and Business M eetings w ill be announced weekly.

SYLLABUS FO R T H E SPRIN G TERM
T h e honorary editorial board and Miss Harkins and M rs. Thom pson once more de serve undying gratitude. W e thank them again for their help and advice which they are always willing to provide.

T H E 232nd S E S S I O N
T h is is the third edition of a popular pocketsized handbook, which originated from three articles written by D r. T u rner for R es M edica in 1 960. T h e expansion of the text has greatly enhanced its com prehensibility, though the changes in the diagrams have not significantly elevated them beyond their form er m edi ocrity. D r. T urn er once again emphasises the need for a m ethodical approach to auscult ation, entreating that the student listen to only one thing at a time. H e underlines the point b y considering the events of the cardiac cycle in turn, passing from heart sounds to systolic and then to diastolic murmurs. M icrobial T axonom y is a subject that few people show any inclination to venture into very deeply. Th ose who do are faced with outstanding problem s in the classification, nom enclature and identification of m icro organisms. S. T . C ow an has actively particip ated in the International C om m ittee on Bacteriological N om enclature which was form ed to discuss the problem s involved in taxonom y.
In this text 'A D ictionary of M icrobial Taxonom ic U sage', he has contributed further with a concise, account of taxonom ic study as it is today. T h e book brings to the forefront the difficulties and pitfalls of bacteriological taxonom y and includes explanatory notes on the various attem pts to design a successful taxonom ic scheme.
M oreover, C ow an has defined principles that require to be followed in the laboratory and particularly in the literature, stressing these in respect of rules form ulated at the m eetings of the International C om m ittee. A unique and sensible present ation that brings to one's attention the attem pts being m ade to bring order to the chaos of bacteriological taxonomy.
G .G .C . T h is is a series of forty short papers, by cardiologists from all over the globe, presented to a sym posium on M yocardial Infarction held in Edinburgh in Septem ber 1967.
T h ese articles are concerned w ith the m any aspects of the treatm ent of acute infarction, ranging from artificial pacing and specialised coronary care units, to digitalis and diuretics. Particularly interesting are those papers in which cardiac arrhythm ias are considered. In the discussions, which are liberally interspersed am ong the proceedings, other participants in the symposium have an opportunity to air their views; m any old questions are answered, while new ones are posed and considered.
O ne would require m ore than a casual in terest in the subject to get very m uch out of this book.
D .M c L . Sir D errick D u n lo p was one of th e m ost well-known of teachers in the Ed in b u rgh M edical Sch ool, and his active days as Pro fessor of T h erap eu tics here are rem em bered with affection and gratitude by his students. W e rarely see him in person now-, b u t he still contributes to our m edical lives to a signifi cant degree, in print.
T h e well-known textbook of M edical T re a t m ent, edited by Sir D errick and by Professor Stanley A lstead now reappears two years after the old edition, in a retread version. T h e old layout has been abandon ed in favour of a double-colum n page, giving Livin gston e's a new, transatlantic look.
T h e vast know ledge of its team o f Scottish contributors guarantees that the book rem ains as com prehensive and as authoritative as ever, new sections on anti-coagulants and iatrogenic effects, and a glossary of drug nam es, having been added. T h e whole thing is as up to date as a textbook can be.
T h e book is recom m ended to anyone with aspirations in m edicine, and upholds the very fine standard set b y previous editions.
J T h is m onograph, designed for m edical practitioners, contains nine chapters, each deal ing with different aspects o f disease in relation to driving. It also includes an appen dix on 'U nw anted and dangerous interactions b e tween drugs'.
O f particular interest are the chapters con cerned with cardiac conditions and with ageing, problem s which affect a sizeable proportion of the driving population. Professor M ary Pickford is the principal auth or of the ch apter on fatigue and boredom , a factor of increasing im portance in these n om adic days of m echan ised transport. Particularly good are the sec tions on 'Suggestions and advice to p atien ts' for they provide, in considerable detail, a well reasoned approach to this often neglected asp ect of patien t care.
T h e little tim e spen t in studying this pam phlet would n ot be wasted for either student or practitioner.
T h o u gh this book is definitely for the specialist, it leaves the non-specialist reader with an uneasy awareness of the chem ical hazards in the environm ent. M o st of us live with the suspicion that the surfeit of new substan ces around us m ay include m olecu les m iching m allecho; bestow ing ills tum ours and m onsters.
T h ese review articles sum m arise w hat is known in this gloom y area of biology.
T o x ic substances, their access to the hum an organism , their im m ediate or delayed e ffects and their visitations upon our children and upon our children's children, arc reported with detached scholarship.
T h e scope is wide, ranging from the dangers of food additives ('all will agree that cancer-causing agents should be avoided in foods wherever p ossible'), to the inevitable self-inflicted tobacco injury ('the m o st p oten t known carcinogen operating on m an at the present tim e is cigarette sm oke').
R ead it, and scare your friends! C .T .C . T h e authors of this excellent book have culled their extensive experience from m any years of research in the field of vascular disease; including work at K in g's C ollege H ospital and at the research establish m en t of the Royal C ollege of Surgeons of E n glan d . T h ey have now published a textbook on this subject, which is b oth lucid and interesting. It covers all aspects of vascular disease, and includes an introductory chapter on the assessm ent of the vascular patien t which is enorm ously helpful to m edical students, especially to those approaching clinical m edicine for the first tim e. D iagnosis, special investigations and the in dications for conservative or for surgical treat m ent are m ade abun dan tly clear and reason able. T h e presentation of the book is, on the whole, a clinical and practical one which m any of its stu den t readers will appreciate.
T h e illustrations and diagram s are very good, appropriate and illum inating and the style is crisp, concise and readable. F rom this book one m ay painlessly absorb a great deal of knowledge, and yet read it with pleasure and enjoym ent.
T h is w ell p lan n ed and e x p lic it p u b lication m u st be o f in terest, and o f sub stan tial value, n o t on ly to th e postgrad u ate fo r w h om it was p rim arily p ro d u ced , b u t to a greater p ro po r tion o f sen ior m ed ical stu d en ts than was in itially envisaged.
T h e in tro d u cto ry ch apters are in fo rm ativ e and in teresting, and those fo llo w in g p resen t a logical an d very co m p le te discussion o f the evalu ation o f the in fo rm atio n availab le from radiographs.
M a n y sen ior studen ts m ig h t b en e fit from such a co n cise in tro d u ctio n to the su b ject and the m ore ad van ced in form ation fo llow s very readily fo r those pu rsu in g p ost graduate courses o f study.
It is to b e h oped that th e d au n tin g cost of this b ook does n o t lim it th e circu latio n , p lacin g it on the sh elves o f referen ce libraries only and thus ren dering it less easily availab le to the readership it p ro p e rly deserves.
M .J .R . L it tle m ore than a d ecad e ago it was show n fo r th e first tim e th at the n orm al h u m an cell con tain s not 48 chrom oso m es b u t 46.
T h e M .R .C . u n it in E d in b u rg h is today th in kin g in term s o f karyo typ in g w h ole p o p u latio n s at birth b y a fu lly au to m ated system u tilizin g advan ced tech n iq u es and sop h isticated com p u te r pro gram m in g. T h is is a m easu re o f the explosion w h ich has occurred in gen etics in recen t years and an in d ication o f th e lik e ly im p act on m e d icin e in the fu ture.
H an d in hand w ith cyto lo gical advances h ave g o n e those in b io ch em ical un derstan din g and P rofessor Em ery has attem p ted to relate the altered position in gen etic k n o w led g e to the needs o f m edical p ractice today. In this h e has m et w ith great success an d both stu d en t and ph ysician are p ro vid ed w ith a co m p re h e n sive acco u n t o f the fu n d am en tal changes in un d erstan d in g w h ich have occurred in relation to in d ivid u al, fam ily and p o p u latio n .
It is a trib u te to the au th o r that he has been ab le to cover the w id e field o f m ed ical genetics w h ilst k eep in g tech n ical term s to a m in im u m . T h e result is both readab le and in stru ctive and exten sive references at the end o f each ch ap te r en ab le topics in w h ich especial in terest has been created to b e easily pursued fu rth er. P .D .B . T h o m a s F u lle r 's d ictu m th at " L e a rn in g hath gain ed m ost by those books b y w h ich the prin ters have lo st" is sure to be refu ted once m ore b y this latest ed ition o f T h e P rin cip les and P ractice o f M e d ic in e . T h e nin th edition is sim ilar in style to the eig h th , em ph asis b ein g on those com m on disorders en cou n tered in p ractice w ith preced in g su m m ary o f the an ato m y and p h ysio lo gy relevan t to each sec tion. U se fu l ad d ition s app ear in the chapters 011 N u tritio n al D isord ers, D iseases o f the Pan creas and D iseases o f the L iv e r and B iliary T ra c t. P rofessor C a rsta irs' rew ritin g o f the P sych o logical M e d ic in e section is d irected tow ards the n eu rotic and p sych osom atic sym p to m at o logy lik e ly to be en cou n tered by the n o n specialist physician in day to day practice. A short resum e o f p sych o tro p ic drugs is an ad d ition w h ich recognises that both m edical and illicit use o f these agents should be fam iliar to every practition er.
T h e u p d atin g o f all section s has n ot led to an y increase in length and desp ite the sligh t price in crem en t this is a b ook w h ich m u st h ave high claim to b ein g perhaps the best valu e am on gst general m ed ical texts n o w avail able.
Develpoment of the Brain by W. A. Marshall.
M o s t m ed ical studen ts q u ail a t the th o u g h t o f learn in g n eu ro an ato m y a fte r h avin g sp en t a year stu d yin g system atic an ato m y in their second year. C o n se q u e n tly all new texts on this su b je c t are eagerly aw aited , scann ed, and then usu ally rejected. L e t there be no d ou b t that this is not an exam in ation -cram m in g book; rath er a lu cid vo lu m e p u rely for leisure readin g -it does not even have an in dex. It does h o w e ve r succeed in w h at it sets ou t to do. It provid es a very e lem en tary p ictu re o f brain d e ve lo p m e n t and in clu des a con sider ation o f brain-w aves, n eu ro b io ch cm istry and the in flu en ce o f the en docrin e system on cerebral d e ve lo p m e n t an d m etabolism .
F o r the asp irin g n eu rop h ysiologist this w ork is n o t adeq uate; fo r the average m ed ical stu d ent it is a usefu l little book.
In this m onograph Professor Ja m es attem pts to assist the young orthopaedic surgeon by presenting a careful review of the confused literature on scoliosis. Assessing his subject with the authority gained from twenty years of practising interest and drawing on research from the Edinburgh O rthopaedic Service, he first defines the term inology of scoliosis, aided by well-chosen radiographs and by clinical photography. H e then proceeds to consider the differential diagnosis, actiological evidence, classification and treatment. Includ ed also are notes on the inheritance of scoli osis and on its m edical aspects. T h e treat ments discussed are those which involve special im m obilisation and traction and also the definitive surgical correction. T h rou gh out the book stress is laid on the im portance of the surgeon's relationship with both the patient and the parent, in w hat m ay be a protracted period of orthopaedic supervision.
Progressive idiopathic scoliosis deforms cruelly and shortens life by its cardio-respiratory consequences. Early recognition is thus para m ount and the undergraduate w ill find it valuable to read the earlier chapters. H e will not regret the tim e spent and will enjoy a book which is marked by its clarity of language and organisation, and by the quality of its illustrative photographs, which are well in tegrated with the text. Professor Jam es' style is attractive and dogmatic, though always supported by evidence. His book should arm well the postgraduate who progresses to the wider literature on scoliosis, to which he will find full references are given.
Blackw e ll Scientific Publications L td . wish to announce that their n ew catalogue for 1968/69 has just been p u blish ed and is avail able from them w ithou t charge.
C orrespondence should be addressed to B lackw ell Scientific P ublications L td ., 5, A lfred Street, O xford.

(S ee page 27)
A . T h e lesion lies in the left basal ganglia and neighbouring stru ctu res: the left cortico spinal tract at the level of the internal capsule, the som atic sensory system in the region of thalamus and the hypothalam us (change in appetite, weight gain, excessive thirst). T h e m ost probable lesion is neoplasm.
B. T h e ventricular system would be distorted by a mass lesion in this region, and lum bar air encephalography is therefore indicated. This confirmed the site of the lesion, but suggested that it m ight arise from the brain stem. V e rte bral angiograms were therefore taken, and showed an aneurysm on the trunk of the left posterior cerebral artery. T h e region which filled with dye was not large enough to pro duce the distortion seen in the encephalograms and it was therefore concluded that the aneur ysmal sac was large, but m ainly filled with thrombus.

C . A cute hepatic failure.
A t autopsy the liver showed a gross macronodular cirrhosis, m ost probably due to previous subclinical virus hepatitis.
N othing in her history or exam ination suggested the presence of cirrhosis, and the earliest developm ent rais ing the possibility of liver disease was the abnorm al bleeding tendency noted at the first operation.
A large aneurysm was found arising from the trunk of the left posterior cerebral artery and extending upwards and backwards into pos terior hypothalam us, left basal ganglia and brain stem : there was extensive destruction of brain tissue and such a lesion would inevit ably -have carried a fatal prognosis, without the additional problems arising from her liver disease.
T h u s although neoplasm is the com m onest lesion in this site the possibility of vascular lesions such as aneurysm or angioma should also be considered.

A ck now ledgm ent
T h is patient was under the care of Professor F . J. G illingham and his permission to report this case is gratefully acknowledged.