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pulmonary hypertension. ENTICKNAP 28 found thatarteriolar sclerosis in the lungs was not alwayspreceded by capillary dilatation, and he suggestedthat the organic arteriolar changes depended on

pulmonary arterial, rather than venous, hypertension.But absence of hyalinisation (which characterises thesystemic arterial lesions produced by hypertension)in all -his cases led ENTICKNAP to postulate that

pulmonary and systemic arterioles might differ funda-mentally. In 4 of his cases thrombi were found in the

arterioles, and these thrombi might have accountedfor the sclerosis. Possibly repeated thromboses or

thrombo-embolism may account partly for thearteriolar changes, but - conclusive proof is lacking.Rheumatic arteritis in the main pulmonary arteries,and occasionally in the smaller branches, has beenreported,29 30 but this is unlikely to play any impor-tant part in bringing about arteriolar sclerosis or

pulmonary hypertension. 20 31

Scalpel in the Surgery ?THE amount of minor surgery met with in general

practice may vary a little, according to the type ofpractice and the kind of industries in the locality ;but the attitude of the practitioner to its performancevaries very widely. To some it is a skill to be developedand increased, while to others it is a time-consuminghindrance to the proper work of the day.

Perhaps not very long ago the practitioner of

today was himself a final-year student or a house-man taking his part in the busy routine of casualtyand surgical outpatients, gaining experience and

judgment as well as dexterity in the lesser surgicalprocedures left to him by colleagues whose eyes wereon higher planes of surgical achievement. Thesebaceous cyst, the circumcision, the localised abscess-these opportunities are met with often enough ingeneral practice to encourage any practitioner whowants to maintain his skill and to gain the addedsatisfaction of seeing his own patient through yetone more clinical adventure. In the country-townpractice (where there is an operating-theatre at thecottage hospital), in the few prototype health centres,and in a few group-practice units, there may be" minor ops " theatres equipped to a standard of

efficiency that the single-handed practitioner cannotachieve. In urban practice, however, where grouppractices are less common, practitioners will under-take their own minor operations less often. As theitems of service making up a day can usually berearranged to enable a desired object to be achieved,we must presume that it is not simply the lack oftime that discourages such work, but a combinationof factors including inadequacy of premises (a satis-factory examination room is not necessarily a goodtheatre), difficulty in getting the help of an anoes-thetist, absence, of a recovery room, and often lackof the trained nursing help which makes the main-tenance of strict surgical sterility practicable. Forsuch reasons many family doctors, though well ableto do their own minor surgery competently, refertheir patients to the casualty department of their28. Enticknap, J. B. Ibid, 1953, 6, 84.29. Kugel, M. A., Epstein, E. J. Arch. Path. (Lab. Med.) 1928,

6, 247.30. Gross, L. Amer. J. Path. 1935, 11, 631.31. Friedberg, C. K. Diseases of the Heart. Philadelphia, 1949.

local hospital. They know that the operation willbe performed there in technically satisfactory circum-stances, though the attendance may be a considerableinconvenience to the patient and the operation anuisance to the casualty officer.

In the valuable article which we publish this week,Dr. J. H. HUNT develops a principle which, if appliedin the larger hospitals, might resolve the difficultyto the advantage of both hospital and practitioner.It should not be impossible to establish, at hospitalswith large casualty departments, a minor-operationstheatre where visiting general practitioners could dotheir own minor surgery. Such a department couldbe efficiently staffed and equipped, and the servicesof an anaesthetist should be easily forthcoming.Local circumstances would determine whether allthe work of a department such as this would be doneby doctors on their own patients,’ or whether, as

Dr. HUNT suggests, a "

general-practitioner specialist"should be appointed on a sessional basis. Either

way, the casualty officer would be relieved of muchnon-casualty work which he may find hard to fitinto a programme not designed for it.

There are all too few links between the large hos-pital and the general practices that feed it, and ifthis* one were to be forged it might do great good.It is in casualty that the young hospital residentsees what he takes to be examples of the inefficiencyand ineptitude of the family doctor. It would bebetter for him if he were taught his minor surgeryby a competent general practitioner who could givehim an understanding of the background to what-ever surgical procedure is undertaken.

Annotations

TRIUMPHS FOR CHEMISTS

Two notable pieces of chemical research have beenannounced that are of direct interest to medical men.The first of these (as already noted briefly in these

columns’) is the elucidation of the structure of themolecule of vitamin B12’ or cyanocobalamin as it is

officially named. Isolated and introduced to medicineseven years ago, vitamin B12 is exceptional among bio-logical substances of importance in human nutritionbecause it contains cobalt. It is now well known thatthe vitamin is essential for the proper development oferythroblasts, and the commonest disease in this countrywith which it is connected is pernicious anaemia. Inthis disease the vitamin is not absorbed, and the ansemia.is relieved by administering the vitamin parenterallyin very small doses, measured in microgrammes.The elucidation of the chemical nature of vitamin B,2

has resulted from a combination of crystallographicwork at Oxford, calculation at Los Angeles, and chemicalstudies at Cambridge and the Glaxo Laboratories atGreenford, Middlesex. The crystallographic part wascarried out by Dorothy Hodgkin and her colleagues.To the uninitiated some of the diagrams that illustratetheir paper look like maps of London’s Underground,and others appear to belong to, space fiction. - We arenot surprised to learn that Dr. Hodgkin and her colleaguesat Oxford had to call in Californian cybernetic assistancein the shape of SWAC (National Bureau of Standardswestern automatic computer) to help them with theircalculations. The formula they eventually proposed wascomplex and represents a considerable achievement for1. Lancet, Aug. 20, 1955, p. 402.2. Hodgkin, D. C., Pickworth, J., Robertson, J. H., Trueblood,

K. N., Prosen, R. J. Nature, Lond. 1955, 176, 325.

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crystallography. " To be able to write down a chemicalstructure very largely from purely crystallographicevidence on the arrangement of atoms in space-andthe chemical structure of a quite formidably largemolecule at that-is," they say, " for any crystallo-grapher something of a dream-like situation." The

crystallographic data by themselves left a number of

points in doubt, and these have been tested and largelyresolved by the workers at Cambridge and Greenford,3who used regular chemical methods. An interestingfeature of the molecule of vitamin B12 (C63Hgo014N14PCO)is the cyclic grouping round the cobalt atom, which isthat present in the porphyrins.The second chemical triumph is the determination of

the structure of the insulin molecule. Insulin proved amuch harder problem than vitamin Bm and ten yearshave elapsed since Sanger and his colleagues at Cambridgepublished their first paper on this subject. The detailsnow described by Sanger et awl. show that, comparedto vitamin B12, insulin has an enormous molecule withthe empirical formula C254H377075N 65S6’ giving a

molecular weight of 5733-5. The structure of the moleculeconsists of two parallel straight polypeptide chainslinked by sulphur bridges that are parts of cystineresidues. These two polypeptide chains are not, as

might be expected, equal in length ; the upper chaincontains 21 units and the lower chain 30 units (countingeach cystine residue as 2 cysteine units) ; so the insulinmolecule must be askew in some manner, possibly coiled.Analysis of the amino-acids present in the moleculeshowed that leucine occurs most frequently at six times,valine five times, glutamic acid, glycine, and tyrosinefour times, aspargine, alanine, cystine, glutamine,phenylalanine, and serine are represented three times,histidine twice, and arginine, lysine, proline, and threo-nine only once. Notable absentees are methionine and

tryptophane. The exact arrangement of these amino-acids in the two parallel chains has been worked out indetail by Sanger and his colleagues-a very strikingpiece of chemical detective work. The Cambridge grouphave also shown 5 that there are small differences in the

composition of the polypeptide chains of the insulinsof different species ; cattle, pig, and sheep insulinsdiffer from each other in this way.The elucidation of the structure of insulin and

vitamin B12 may point the way to their eventual synthesis.The supply of cortisone has depended on chemical know-ledge of the structure of the drug and its partial synthesis.But for both vitamin B12 and insulin we have efficientbiological sources, the use of which has been brought toa high degree of perfection. Moreover these substancesare produced remarkably inexpensively. A diabetic

patient on 40 units of insulin zinc suspension dailyuses about 7 pennyworth of insulin ; while for the patientwith pernicious anaemia on 100 (j(.g. vitamin B12 weeklythe cost is about 10d. (the streptomyces that produces thevitamin is a notably efficient organic chemist). The

posterior-pituitary hormones, oxytocin and vasopressin,and at least one of the anterior-pituitary hormones haveknown chemical structures and have already beensynthesised by American workers, but the methods ofsynthesis are not at present suitable for large-scale pro-duction. Yet even if knowledge of structure does notaffect the supply of material for treatment, it is veryimportant. We hope that fundamental information ofthis sort will help us to understand the mode of actionof insulin, vitamin B1, and the others ; it may leadto better treatment and even aid prevention in the longrun. Doctors will watch with unsimulated interest theresults of the efforts of their chemical colleagues, eventhough they may not follow the technical details.3. Bonnett, R., Cannon, J. R., Johnson, A. W., Sutherland, I.,

Todd, A. R., Smith, E. L. Ibid, p. 328.4. Ryle, A. P., Sanger, F., Smith, L. F., Kitai, R. Biochem. J.

1955, 60, 541.5. Brown, H., Sanger, F., Kitai, R. Ibid, p. 556.

SYNTHETIC ARTERIAL GRAFTS

FOR forty years arterial surgery stood where this

century’s early pioneers had left it. Only by local repairwas it possible to reconstruct a major artery. Graftingwith a segment of vein, though occasionally successful,never became a standard method of bridging the longerdefects. In 1949 Gross and his colleagues 1 describedthe clinical application of Carrel’s method of homo-

grafting with the stored arteries of another individual.Since then surgeons all over the world have followed thislead, and major arterial lesions up to and including theaortic arch can now be excised and the artery recon-structed. Such arterial segments are usually dead whenimplanted, and they do not retain their original structurefor long afterwards. Within a few weeks only extra-cellular material (mainly the elastic layers) remains. Themain virtue of the arterial homograft, apart from itssmooth lining and elasticity, seems to lie in its negativefe,i,tures-its inertness and the mildness of the reactionthat it evokes, confined to a slow, healing incorporationwhich secures its function as a major blood-vessel.Human arterial grafts are scarce. Even with per-

manent storage, such as is now possible with deep-freezing 2 and freeze-drying,3 the essential difficulty of

procuring the grafts remains. Other forms of prosthesishave been tried. Intubation of the arterial defect byrigid protheses of metal, glass, or plastic nearly alwaysleads to haemorrhage or thrombosis, though Hufnageland his colleagues 4 have shown that in the thoracic aortaof man and the dog a polished Perspex ’ tube or ball-valve will usually remain patent if fixed by a multi-’

‘

pointed nylon ring at either end. Below this level, andparticularly where the soft tissues are mobile, all methodsinvolving rigid tubes may be expected to fail. A muchmore promising method was introduced by Voorheeset awl. They fashioned tubes of a plastic cloth, VinyonN,’ and sutured these into the dog’s abdominal aorta.The results encouraged them to use the same method inpatients urgently needing operation, and in 1954 theyreported good results after grafting with this material in18 patients, mostly with abdominal aneurysms.6The technique of inserting cloth tubes is much the same

as that of homografting. When the arterial clamps arereleased blood leaks between the interstices of the fabric.The amount of bleeding depends on the material used,its weave, and its water-repellancy. Vinyon N is lesssatisfactory in this respect than finer fabrics such as

’Orlon,’’ Dacron’ (’Terylene’), and nylon. It generallyneeds to be " pre-clotted " by preliminary exposure towhole blood, either in vitro or by prolonging the intervalbetween removal of the distal clamp and removal -of theproximal clamp. A liberal amount of enmeshed fibrin ishelpful in that it provides a medium for the migration offibroblasts, which organise the prosthesis into a livingfibrous tube with a durable cloth reinforcement. Thiswould seem to be an excellent substitute for a homograft :in fact it may prove in some ways even better, for homo-grafts may have a limited life. Degenerative changeshave already been reported in early dog preparations,7but there are so far no reports of late failure in casesgrafted with suitable material by established methods.Arterial grafts have now been applied in several hundredcases, some as long ago as 1948. At St. Mary’s Hospital,London, alone over 100 such grafts have now beenapplied, 40 of them to the aorta. Most of these were

1. Gross, R. E., Bill, A. H., Peirce, E. C. Surg. Gynec. Obstet.1949, 88, 689.

2. Eastcott, H. H. G., Hufnagel, C. A. Surg. Forum, 1950,p. 269.

3. Marrangoni, A. G., Cecchini, L. P. Ann. Surg. 1951, 134, 977.4. Hufnagel, C. A., Rabil, P., Harvey, W. P., McDermott,

T. F. Surgery, 1954, 35, 673.5. Voorhees, A. B., Jaretski, A., Blakemore, A. H. Ann. Surg.

1952, 135, 332.6. Blakemore, A. H., Voorhees, A. B. Ibid, 1954, 140, 324.7. Coleman, C. C. jun., Deterling, R. A. jun., Parshley, M. S.

Surgery, 1955, 37, 64.