1256

after calcification at the right hilum had been present forat least a year. Another (case 5) showed hilar glandenlargement after clearing of a pleural effusion on theopposite side. Wallgren (1948) observed that pleuraleffusion usually takes place 3 to 7 months after theprimary infection and usually on the same side; but in ourpatient the effusion and the glands were on opposite sides,and the glands followed the effusion. Our findings suggestthat, though enlarged mediastinal glands in Asian andcoloured adults may develop at the time of the primaryinfection, the mediastinal adenitis may also occur at alater stage of the disease, which is uncommon in

Europeans.Pinner and Kasper (1932) in postmortem studies on

Negroes found caseous lymph-glands, even in adults withcalcified primary lesions, and concluded that tuberculosisin the Negro produces a high state of allergy but not anincreased resistance. Our observations support the viewthat some Asian and coloured adults fail to develop thesame degree of acquired resistance as the European at thetime of primary infection, so that the subsequent clinicalpicture may present features of both primary and chronicpulmonary tuberculosis simultaneously.

In conclusion, the finding of enlarged mediastinal

glands in an Asian or coloured patient should immediatelysuggest the possibility of tuberculosis; otherwise theremay be unnecessary errors and delays in diagnosis.

SummarySeven patients from India and the West Indies with

mediastinal lymphatic gland tuberculosis are described.The main presenting symptom was pyrexia, together

with some cough and sputum. The course of the illnesswas long with a tendency to relapse. The radiologicalappearances were those of mediastinal glandular enlarge-ment, either unilateral or bilateral, with or withoutassociated parenchymal lesions. The enlarged mediastinalglands showed only gradual response to antituberculousdrugs, compared to the more rapid response of the

parenchymal lesions.The relation of enlarged mediastinal glands in Asian

and coloured adults to primary tuberculosis is discussed.Our findings suggest that, though the mediastinal adenitismay develop at the time of the priinary infection, it mayoccur at a later stage of the disease, which is uncommonin Europeans. Failure to acquire resistance at the time ofthe primary infection may account for a clinical picturepresenting features of primary and chronic pulmonarytuberculosis simultaneously.The finding of enlarged mediastinal glands in an Asian

or coloured patient should immediately suggest the

possibility of tuberculosis.We wish to express our thanks to the consultant staff of the

London Chest Hospital; to Dr. R. M. Orpwood and Dr. W. F.Richards for their kind permission to publish details of their patients;to Dr. Basil Strickland for reviewing the radiographs; and to Mr.A. C. Curd, photographic department, Institute of Diseases of theChest, for the illustrations.

REFERENCES

Benjamin, P. V. (1956) Bull. int. Un. Tuberc. 26, 561.Bentley, F. J., Grzybowski, S., Benjamin, B. (1954) Tuberculosisi n Child-

hood and Adolescence. London.London County Council (1956) Report of the County Medical Officer of

Health and Principal School Medical Officer for the Year 1955. London.Long, E. R. (1937) Amer. Rev. Tuberc. 35, 1.Opie, E. L. (1930) ibid. 22, 613.Pastor, J. R. (1937) ibid. 35, 13.Pinner, M., Kasper, J. A. (1932) ibid. 26, 463.Wallgren, A. (1948) Tubercle, 29, 245.

EXCRETION OF PORPHOBILINOGEN AND

&dgr;-AMINOLÆVULINIC ACID INACUTE PORPHYRIA

BRIAN ACKNERM.A., M.D. Cantab., F.R.C.P., D.P.M.

PHYSICIAN, BETHLEM ROYAL AND THE MAUDSLEY HOSPITALS; PHYSICIANAND LECTURER IN PSYCHOLOGICAL MEDICINE, HAMMERSMITH HOSPITAL

AND THE POSTGRADUATE MEDICAL SCHOOL OF LONDON, W.12

J. E. COOPERB.A., B.M. Oxon., M.R.C.P.

REGISTRAR, THE MAUDSLEY HOSPITAL, LONDON, S.E.5

C. H. GRAYM.D., D.Sc. Lond., F.R.C.P., F.R.I.C.PROFESSOR OF CHEMICAL PATHOLOGY,

KING’S COLLEGE HOSPITAL MEDICAL SCHOOL, LONDON, S.E.5

MARGARET KELLYB.Sc. Grahamstown

RESEARCH ASSISTANT

D. C. NICHOLSONPh.D. Leeds, F.R.I.C.

LECTURER IN CHEMICAL PATHOLOGY,KING’S COLLEGE HOSPITAL MEDICAL SCHOOL

ACUTE porphyria is an inborn error of metabolismcharacterised by attacks of abdominal pain which may beslight, or of such severity as to simulate a surgicalemergency, often in association with neurological andmental symptoms and signs of great variety. During theacute stages, the monopyrrolic compound, porpho-bilinogen (P.B.G.) is excreted in the urine (Waldenstrom1937); and, as has subsequently been shown by Granickand vanden Schrieck (1955), this is accompanied by itsmetabolic precursor, 8-aminoloevulinic acid (A.L.A.). TheP.B.G. excretion during remission may either decrease tolow or negligible amounts (Waldenstrom 1937, 1957), or,according to Watson (1954), continue in about 20-50%of the quantities excreted during the acute stage.

In the patient studied by Granick and vanden Schrieck, therate of excretion remained high during periods in which mildsymptoms or no pain at all were observed, and the onset ofpain was not related to increased P.B.G. excretion. This patientexcreted about 40 mg. of A.L.A. daily-i.e., about 40% byweight of the excreted P.B.G. Lowry et al. (1950) had foundP.B.G. in each of 44 subjects with porphyria, 16 of whom werealso investigated during remission. 15 of the 16 excreted P.B.G.in more than trace quantities; and in 7 cases in which serialobservations were made, the P.B.G. excretion decreased sub-stantially during complete clinical remission. Watson et al.

(1951) emphasised that the P.B.G. reaction sometimes becamenegative during remission, but the qualitative test they usedwas less sensitive for the detection of slightly increasedamounts of P.B.G. than the quantitative measurements by themethod of Mauzerall and Granick (1956). Using this methodHaeger (1958) determined P.B.G. and A.L.A. in the urine of 34patients with manifest porphyria, and in 128 of their closerelatives. Contrary to the earlier report of Hammond andWelcker (1948) who investigated 1000 non-porphyric patientswithout finding P.B.G. in the urine, Haeger found small amountsof P.B.G. as well as of A.L.A. in normal urine. She showed thatall the 34 patients with the overt condition excreted P.B.G. inpathologically increased amounts, and, of these, 29 alsoexcreted increased quantities of A.L.A. Of 7 " geneticallycertain carriers "-i.e., persons whose parent, brother, sister,child, niece or nephew had either latent or manifest porphyria-6 excreted increased amounts of both A.L.A. and P.B.G. whilein the 7th P.B.G. only was increased.

The present study was undertaken to investigate thepossible correlation between variations in the A.L.A. andP.B.G. output and changes in physical and mental state.

1257

At the same time the opportunity was taken to examinein detail the previous personality and life history of theporphyric patients, and these findings will be reportedelsewhere (Ackner et al. 1961).

The Patients

12 patients known to have suffered from acute porphyria wereadmitted to the Maudsley Hospital for a period of two weeksor more for investigation. All except 2 (cases 5 and 12) whohad recurring attacks of a doubtful nature, were in the latentstage on first admission; but 1 (case 3) was subsequentlyreadmitted in an acute attack, and 3 (cases 4, 6, and 10) hadacute symptoms after admission to hospital. 2 further patientswere studied, both apparently in the early recovery stages of asevere acute attack-1 (case 13) in Lewisham Hospital underthe care of Dr. J. Staffurth, and the other (case 14) in King’sCollege Hospital under the care of Dr. J. C. Hoyle. This last

patient was readmitted in an acute attack and was again studieduntil he was well enough to return home. The clinical featuresof these patients are summarised in the appendix.

Chemical Methods

P.B.G. and A.L.A. were estimated by the method of Mauzeralland Granick (1956) which depends on the separation of P.B.G.fr.om A.L.A. on an ion-exchange column followed by estimationof the former with Ehrlich’s reagent and of the latter with thesame reagent after condensation to a monopyrrolic compoundwith acetyl-acetone.

Results

Table I shows the results of the investigations carriedout on the 12 patients admitted to the Maudsley Hospital,with the mean excretion of P.B.G. and A.L.A. in ascendingorder of the combined excretion of these two compoundsin micromoles. The sum of the excretions of A.L.A. andP.B.G. has been given in micromoles because of the differentmolecular weights of these two compounds. The 4 patientswith the highest average excretions of A.L.A. and P.B.G. com-bined (cases 3, 4, 6, and 10) all experienced, during theperiod of investigation, attacks of abdominal pain whichwere probably due to exacerbations of the porphyria. But 3other patients (cases 2, 9, and 11) also had high averageexcretion-rates; and, although 1 (case 2) had some

residual paralysis, none complained of any symptomsduring the investigation and their last porphyric attackhad been some time previously. 2 patients (cases 5 and 12)

TABLE I-EXCRETION OF PORPHOBILINOGEN AND 8-AMINOLE.VULINIC ACID IN THE 12 MAUDSLEY HOSPITAL PATIENTS

who were admitted complaining of abdominal painexcreted r.B.G. and A.L.A. in amounts little exceedingnormal, but in both there were features suggesting thattheir complaints might be largely of psychological origin.Cases 1, 7, and 8 were free from symptoms, and the meanexcretions of P.B.G. and A.L.A. were scarcely raised abovethe normal given by Haeger (1958) although there werefluctuations giving peaks of between two and three timesthe upper limit of normal.

Table II shows the results obtained in the 2 subjectswho at the time of investigation had severe symptomseither of pain or of frank paralysis. Case 13 was firststudied about fourteen days after the beginning of anacute attack. Despite this, the average excretion of P.B.G.and A.L.A. was lower than in the almost symptomlesspatients who were excreting considerable quantities ofthese compounds. Case 14 was first studied when he was

recovering slowly from an acute attack which had occurredseveral weeks previously. He was then excreting lessP.B.G. and A.L.A. than case 6, who, of the other subjectsstudied, excreted the largest amounts of these two com-pounds. However, two days after his discharge fromhospital, reasonably well, he experienced an acute attackand was immediately readmitted for further investigation.He was then studied for ten days during the acute illnesswhen the mean and peak P.B.G. excretions were 109 and171 mg. respectively and the corresponding figures forA.L.A. were 87 and 156 mg. During a subsequent period,the mean and peak excretions of P.B.G. were 132 and250 mg. and of A.L.A. 99 and 156 mg. At this time heseemed dangerously ill, but remission then set in and hisexcretion of P.B.G. and A.L.A. returned to about their

pre-attack levels.All the subjects studied showed variation in the daily

excretion of the two compounds. In some these were

relatively small (see figure, A and B) while in others theywere much larger (see figure, C); no correlation wasdiscernible between the peaks of P.B..G. and A.L.A. excre-tion and the clinical condition; and indeed case 3, whowas studied on the first occasion during remission and ona second occasion after having had an attack of abdominalpain (see figure, D) showed neither a significant difference

TABLE II-EXCRETION OF PORPHOBILINOGEN AND 8-AMINOLE.VULINIC ACID IN 2 SERIOUSLY ILL PATIENTS WITH ACUTE PORPHYRIA

1258

Variations in excretion of porphobilinogen and -aminolaevulinic acid.A and B demonstrate the relatively minor fluctuations in cases 9 and 2. C and D

represent the distinct fluctuations in case 3 during remission and mild attack.

between the mean values nor any obvious change in natureor extent of the variations in excretion of P.B.G. and A.L.A.

Discussion

Relation of P.B.G. and A.L.A. Excretion to SymptomsIn the majority of our patients the diagnosis of acute

porphyria had been suggested by the voiding of urine of acolour varying from pale pink to deep mahogany or whichhad become dark on standing. Porphobilinogen itself is acolourless chromogen, and the freshly voided urine isoften of a normal colour even during the acute attacks.The change to the porphyrins and other coloured com-pounds may occur after acidification and heating or afterthe urine has been standing for any length of time. Thecolour of the urine thus depends on physical factors anddoes not necessarily reflect the concentration of porpho-bilinogen.

It is the occasional coloured urine that often points tothe diagnosis, and it is perhaps this that has led to thewidespread belief that the acute attack of porphyria is

accompanied necessarily by an increased ’excretion of

porphobilinogen. This view receives little support fromthe general pattern of our results, although in cases 1-12excretion of A.L.A. and P.B.G. tended to be greatest in those

patients with the more definite symptoms. The meanexcretion of A.L.A. and P.B.G. and the peak limits attainedduring the acute attack of case 14 were the highestobserved for all the subjects studied. On the other hand,case 13 was very ill and yet excreted quantities of P.B.G.and A.L.A. much lower than other subjects, who werepractically symptomless; and in case 3, who was studiedin relapse as well as in remission, the differences betweenthe levels of excretion during the two stages were insigni-ficant ; indeed, there were days during the symptom-freeperiod when excretion of P.B.G. and A.L.A. was greaterthan at any time during the period of relapse. Cases 5 and12 apparently experienced pain and other symptomsat times when excretion of P.B.G. and A.L.A. was increasedlittle if at all.

Case 2, who had residual weakness and paralysis fromattacks several years previously, excreted significantlyincreased amounts of A.L.A. and P.B.G. although free from

pain at the time of investigation. Case 11was of special interest. He had been freeof symptoms for at least three years before

investigation, yet on admission he was

excreting 92 mg. and 46 mg. of P.B.G. andA.L.A. respectively per day. This level ofexcretion approaches that of the subjectsin relapse, and certainly equals that of suchsubjects on individual days. The highlevel soon decreased during his stay in

hospital. There is thus no doubt that

patients who have had attacks of acuteporphyria can excrete A.L.A. and P.B.G. inmoderately large amounts while remainingwell and free from clinical features of thedisease.

The P.B.G.jA.L.A. RatioIn general the excretion of A.L.A.

paralleled that of P.B.G., and there was noevidence that the A.L.A. excretion or thecombined P.B.G. and A.L.A. excretion

I

reflected the clinical condition any betterthan did the P.B.G. excretion. The ratio ofP.B.G. to A.L.A. must depend on the activity

of the enzyme A.L.A. dehydrase responsible for the con.version of A.L.A. to P.B.G. in the tissues. In health thisratio appears to be less than 1, but in patients with acuteporphyria, as well as in carriers of the porphyria gene, theratio usually increases to above 1 (Haeger 1958), presum-ably reflecting the adaptive increase in the enzymeactivity which Scott (1954) has already shown to be

present in patients with the disease. In case 14 the ratiofell below unity when he was excreting larger quantitiesof the precursors at the time of his acute attack. This

suggests that at this time the body was suddenly floodedwith an amount of A.L.A. which exceeded the capacity ofthe already greatly increased A.L.A. dehydrase activity.Excretion of P.B.G. and A.L.A. in the Acute AttackA severe acute attack might thus be associated for a

short period-perhaps a few days or even hours-with theexcretion of the two porphyrin precursors in much greaterquantities than in the series we have studied. If this were

so, the symptoms experienced by many patients mightrepresent the sequelse of disorder in the nervous systemwhich had occurred earlier at the time of such a "metabolic

explosion ". None of the Maudsley patients can have hadan acute exacerbation of this severity during the period ofstudy. Case 13 at the time of investigation might havebeen in a stage of slow recovery. On the other hand, case14, at the times at which his illness was severe, was

excreting very much larger amounts of P.B.G. and A.L.A.TABLE III-PORPHOBILINOGEN EXCRETION IN SERIOUSLY-ILL PATIENTS

WITH PORHYRIA

1259

than any of the other patients, and there is no doubt thathis acute phase was prolonged. Nevertheless, the defini-tion of what constitutes an acute attack is very nebulous.An analysis of published data and of data kindly madeavailable by colleagues suggests that patients with acuteporphyria can at times excrete much larger amounts ofP.B.G. than we have observed. All 8 patients referred to intable ill excreted much larger amounts of P.B.G. whiletheir symptoms were extremely severe. Unfortunately,A.L.A. was not measured in any of these cases. On theother hand Goldberg (1954) has described 2 cases of acuteporphyria in which 52 and 250 mg. P.B.G. was excreteddaily during brief periods of freedom from pain. He hasalso described 2 patients excreting 120 and 100 mg. P.B.G.;1 had recovered fully from a previous attack, while theother never had symptoms referable to porphyria. TheP.B.G. content of the specimens of urine removed postmortem from 4 of Goldberg’s subjects was probably veryhigh. However, the urine passed the day before deathby 1 of his patients, and a postmortem specimen from anunpublished case examined by one of us (C.H.G.), con-tained only 19.6 and 12 mg. P.B.G. per litre respectively.It cannot, however, be excluded that in these 2 casesterminal renal failure prevented the excretion of P.B.G.in high concentrations in the urine.

It seems unlikely that there can be a direct causalrelation between symptoms and P.B.G. and/or A.L.A.

excretion. Berlin et al. (1956) found that administrationof A.L.A. to normal men, while causing excretion of amountsof A.L.A. and P.B.G. comparable to those occurring in acuteporphyria, did not cause the clinical symptoms of thedisease. In patients with the disease, A.L.A. did not causeworsening of symptoms. Neither P.B.G. nor A.L.A. cantherefore be toxic, and it seems probable that the excretionof the two metabolites and the nervous system changes areseparate manifestations of a metabolic event or series ofevents.

Diagnosis of Acute PorphyriaFrom the clinical point of view porphyria is a deceptive

and frequently misdiagnosed condition. The early symp-toms are both varied and variable, and are often un-accompanied by physical signs. Being a rare disorder, it isseldom diagnosed at an early stage. The abdominal pain,vomiting, nausea, and constipation may, even in theabsence of pyrexia, leucocytosis, and abdominal rigidity,lead to a tentative diagnosis of a surgical emergency; andan exploratory laparotomy with negative findings usuallyresults in the diagnosis of a functional disorder. Com-plaints of weakness of the limbs, with variable aches andabdominal pain unassociated with demonstrable physicalsigns, commonly cause hysteria to be diagnosed; and thisdiagnosis has been retained even when advanced paralysisdue to porphyria has been present for some time. Theimpression that the complaints of the porphyric patientare functional rather than organic is often reinforced bythe accompanying signs of emotional instability; and ifthese give way to a frankly psychotic state, admission to amental hospital is the usual outcome. It is therefore

proper that the literature relating to the clinical aspects ofporphyria should repeatedly contain warnings of thedangers of dismissing certain phenomena as hysterical,and so failing to make the correct diagnosis.On the other hand, our results indicate that the finding

of porphobilinogen in the urine of a patient with suggestivesymptoms does not prove the diagnosis of acute porphyriafor quite a high excretion-rate may occur in symptomless

cases and mild attacks may be accompanied by no increasein output. In 4 of our patients (4, 5, 10, and 12) environ-mental stress was present; and indeed some workers haveclaimed that emotional factors can precipitate attacks.Elsewhere we report in detail findings which suggest thatin many such patients either the stress is coincidental or theattack itself is largely a hysterical reaction to the stresswith the porphyric process playing little or no part(Ackner et al. 1961).The diagnosis of the mild attack presenting with no

demonstrable physical signs is therefore a matter for clini-cal judgment, often requiring skilledpsychiatricassessment.

SummaryThe urinary excretion of porphobilinogen (P.B.G.) and

8-aminolaevulinic acid (A.L.A.) has been measured and

compared with the clinical findings in 14 patients with,acute porphyria.Although there was a rough correlation between severity

of symptoms and excretion of P.B.G. and A.L.A., somepatients excreting considerable quantities of these com-pounds were symptomless, while others with no greatlyincreased excretion of P.B.G. and A.L.A. had symptoms.The excretion of these two compounds fluctuated con-

siderably, but there was no correlation between peaks ofexcretion and acute symptoms.There was evidence that at times patients with acute

porphyria excrete very large quantities of P.B.G. and A.L.A.,and that these very high levels of excretion may be main-tained for only a relatively short time.The excretion of these two metabolites and the changes

in the nervous system are separate manifestations of ametabolic event or series of events.

Porphyric patients can present with symptoms whichare a psychogenic reaction to environmental stresses, andthe level of porphobilinogen in the urine does not assistin the diagnosis of the acute attack in such cases.We are grateful to Professor C. Rimington, F.R.S., and Dr. A.

Goldberg for making available some results of analyses in cases ofporphyria.We are grateful to Dr. J. Staffurth and Dr. J. C. Hoyle for their

permission to investigate cases 13 and 14 respectively, and for pro-viding details of these cases.We also thank the Mental Health Research Fund for a personal

grant to one of us (M. K.) and for an expenses grant to cover specialapparatus and equipment. Miss Jacqueline Newman gave skilledtechnical assistance and helped with some of the statisticalcalculations.

REFERENCES

Ackner, B. G. C., Cooper, J. E., Gray, C. H., Kelly, M. (1961) To bepublished.

Berlin, N. I., Neuberger, A., Scott, J. J. (1956) J. Biochem. 64, 80, 90.Goldberg, A. (1954) Lancet, ii, 1095.

— (1959) Quart. J. Med. 28, 183.Granick, S., vanden Schrieck, H. G. (1955) Proc. Soc. exp. Biol., N. Y. 88,

270. Gray, C. H. (1950) Arch. intern. Med. 85, 459.Haeger, B. (1958) Lancet, ii, 606.Hammond, R. L., Welcker, W. L. (1948) J. Lab. clin. Med. 33, 1254.Kelényi, G., Arato, G., Buda, V., Orbán, S. (1960) Lancet, i, 434.Lowry, P. T., Schmid, R., Hawkinson, V. E., Schwartz S., Watson, C. J.

(1950) Bull. Univ. Minn. Hosp. 22, 97.Mauzerall, D., Granick, S. (1956) J. biol. Chem. 219, 435.Scott, J. (1954) in Porphyrin Biosynthesis and Metabolism (edited by

G. E. W. Wolstenhome and Elaine C. P. Millar). London.Shemin, D. (1956) in Currents in Biochemical Research (edited by D. E.

Green). London.Sveinsson, S. L., Rimington, C. (1950) Scand. J. clin. Lab. Invest. 2, 209.Waldenström, J. (1937) Acta. med. scand. suppl. 82.

— (1957) Amer. J. Med. 22, 758.Watson, C. J. (1954) Advanc. intern. Med. 6, 235.

— Lowry, P. T., Schmid, R., Hawkinson, V. E., Schwartz, S. (1951)Trans. Ass. Amer. Phycns, 64, 345.

AppendixCLINICAL FEATURES OF PATIENTS

Case 1.—Female, aged 47. Abdominal symptoms, mentalchanges, and paralyses after barbiturates 6 years before.During investigation mental state normal; no pain but mildresidual weakness of feet.

1260

Case 2.-Female, aged 45. 8 years earlier abdominalsymptoms, mental disturbance, and paralyses leaving residualclaw-hands and partial foot-drop. Normal during investigationapart from brief periods of depression or anxiety.Case 3.-Female, aged 37. Several attacks of abdominal

symptoms, mental change, and weakness over 5 years. Duringfirst investigation no symptoms. During second investigationabdominal symptoms, fatigue, and depression but no physicalabnormalities.Case 4.-Male, aged 37. Severe attack of abdominal

symptoms and pareses 6 years previously. Subsequent attacksof abdominal symptoms and depression. Three bouts ofabdominal symptoms during investigation. First two coincidedwith peaks of porphobilinogen excretion.Case 5.-Female, aged 57. Many attacks of abdominal

symptoms with depression and hallucinations over 12 years.During investigation repeated abdominal symptoms andweakness with rapid recovery, some probably hysterical.Case 6.-Male, aged 44. Attacks of abdominal symptoms

for 15 years; severe paralysis with slow recovery 5 years beforeinvestigation. Residual bilateral claw-hand and foot-drop.Bouts of mild abdominal symptoms but mentally normal duringinvestigation.Case 7.-Female, aged 48. Confusion with mental defect

and epilepsy since childhood. No other symptoms.Case 8.-Female, aged 60. Attacks of abdominal symptoms

with weakness of arms and paralysis of legs for 6 years. Duringinvestigation no symptoms of porphyria.Case 9.-Male, aged 61. Attacks of abdominal symptoms,

depression 14 years and 2 years earlier. No symptoms of

porphyria during investigation.Case 10.-Female, aged 23. Attack of abdominal symptoms

1 year before admission; further attack 2 days after admission.Mental condition constantly changing during period of study.Case 11.—Male, aged 36. One attack of abdominal symp-

toms 3 years before. During investigation no physical or mentalabnormality.Case 12.-Male, aged 20. Attacks of severe abdominal

symptoms for 1 year. Abdominal pain and apparentlyhysterical fits during investigation.Case 13.-Female, aged 26. Attacks of abdominal symptoms

for 10 years. Extensive muscular weakness with paralysesduring and for two weeks before investigation.Case 14.-Male, aged 22. Abdominal symptoms for 3

months. Mental state normal at first investigation. Readmittedwith weakness. Severe mental symptoms but no abnormalneurological signs.

THE USES OF GLASSONADAVID F. THOMASM.B. N.U.I., F.R.C.S.

SENIOR ORTHOPÆDIC SURGEON,COUNTY AND ST. GEORGE’S HOSPITALS, LINCOLN

SPUN-GLASS and cellulose-acetate fibres, woven togetherand then knitted circularly (like stockinette), are suppliedas bandages 3 yards long and 3 or 4 inches wide under thetrade name of ’ Glassona’. After immersion in either

acetone, which is inflammable, or a mixture of methylenechloride 99-25% with industrial alcohol 0-75%, whichis non-inflammable, the cellulose acetate dissolves. The

bandage is then in a pliable state in which it can bemoulded easily to a surface and one layer will bond toanother. As the surplus acetone evaporates, the spunglass hardens. The material so produced has certaincharacteristics which make it very suitable for ortho-

paedic splints. Plaster-of-paris has become so establishedas the material of splints that we tend to be complacentabout its virtues; but we should. not neglect to search forsomething better. Glassona is lighter and more durablethan plaster-of-paris, impervious to water, and trans-

lucent to X rays. If distorted it regains its shape, so thata forearm or trunk splint can be sprung open after cuttingdown one side, removed, and then replaced without lossof fit or rigidity.DisadvantagesAlthough available for seven years, glassona has not

become widely used. It has one major disadvantagewhich discourages its routine use for splints-namely,that at room temperature rigid setting is not achievedfor 3-4 hours. By means of a hot air drier the setting timeof small splints can be accelerated to 15-30 minutes, buteven this is too slow for the treatment of displacedfractures. The long setting time and the inconvenienceof using a dryingmachine dis-

courage the use of

glassona whether

manipulation isinvolved or not.

Even with theaid of a dryingmachine it wouldnot be safe to

move a patient ina glassona hip-spica off the frac-ture table in lessthan an hour.The danger of

using inflam-mable solvent inassociation withan electricalmachine is ob-

vious, but I donot believe thatthis has prevented more widespread use of glassona.The risk can be lessened by safe electrical equipment andby free ventilation to disperse the acetone vapour;ventilation is necessary, too, to prevent acetone sickness.With these precautions the routine use of glassona is nomore fraught with danger than many common medicalprocedures-e.g., the use of inflammable anmsthedcagents.

Combined Glassona-plaster SplintsThe reason why glassona has not become popular as a

splinting material in routine orthopaedic work is due moreto its long setting time than any other consideration.I have tried to counteract this disadvantage by combiningglassona with plaster-of-paris temporarily or permanentlyin the making of splints, and in seven years’ use I havefound this to be of great advantage and without undue risk.My method is to use a light cast of plaster to stabilise

the part to be splinted. The glassona fraction of the splint

Fig. 1-Combined glassona-plaster spica.

Fig. 2-Outer plaster shell being removed to leave a glassona splint-