Human amniotic membrane: a versatile wound dressing

JOSEPH S. GRuss,* MB, B CH; DENNIS W. JIRSCH, MD, M SC, PH D, FRCS[C]

Human amniotic membrane proved tobe a versatile and useful temporarybiologic dressing in studies involving120 patients. Wounds, both traumaticand nontraumatic in origin, respondedto a protocol that allowed coverageof tissues as diverse as exposed bowel,pleura, pericardium, blood vessels,tendon, nerve and bone. Woundsunresponsive to usual therapeuticmeasures responded to membraneapplication. Ease of availability, negligiblecost and facilitated wound healingmake this temporary biologic dressinggenerally superior to either cadaverskin allograft or pigskin xenograft.Human amniotic membrane dressingsare therefore a useful adjunct in thecare of the complicated wound.

Dans des etudes impliquant 120 patientsIa membrane amniotique humaine s'estav6r6e un pansement biologiquetemporaire utile et versatile. Lesblessures, traumatiques ou non, ontr6pondu a un protocole qui prevoyaitle recouvrement de tissus aussi diversqu'un intestin, une plevre, un pericarde,des vaisseaux sanguins, un tendon,un nerf ou un os mis & nu. Desblessures ne reagissant pas aux mesuresth6rapeutiques habituelles ont repondua une application de membrane. Sagrande disponibilit6, son coOt negli.geable et son effet b6n.fique sur Iacicatrisation des blessures rendent cepansement biologique temporairegeneralement superieur aux allogreffesde peau d'origine cadaverique ou auxxenogreffes de peau de porc. Lespansements de membrane amniotiquehumaine constituent donc une mesured'appoint utile dans le traitementdes blessures compliquees.

The main goal in management of anopen wound is to obtain a clean andclosed wound in the shortest time.Deleterious effects of an open woundare many and are related mainly tothe size and site of the wound. Fluid,

From the department of surgery (divisionsof plastic surgery and general surgery),University of Toronto and the departmentof surgery, St. Michael's Hospital,Toronto*Resident at St. Michael's, St. Joseph'sand Toronto Western hospitals whilethis study was performed.Reprint requests to: Dr. Dennis W. Jirsch,55 Queen St. E, Ste. 407, Toronto, Ont.M5C 1R6

heat and nutrient loss, continuingcontamination and sepsis, and as-sociated pain and decreased mobilitymay seriously hamper patient recov-ery, and early coverage of a majorburn wound may be lifesaving. Thesearch for an ideal wound cover as asubstitute for the patient's skin beganmore than a century ago and contin-ues today. In the late 1 800s Gird-ner,1 Reverdin2 and Lee3 used cadaverand animal skin to cover burnwounds. Davis4 in 1910 reported at-tempts to graft pieces of amnioticsac onto granulating wound, and 3years later Sabella5 described thetreatment of a burned patient withportions of amniotic membrane.

These early attempts at substitu-tion for the patient's skin were de-signed to provide permanent coverageand failed because of immunologicrejection. Years later Dogo6 initiatedthe use of split-thickness cadaver skinallografts as temporary biologic dress-ings for large burn wounds, a proce-dure popularized by Brown and as-sociates.7 Removal of such dressingsand replacement with another skinallograft or an autograft prior to re-jection was an important factor inthe increasing rate of survival frommajor burns. The rejection reactionis unpredictable and occurs unevenly.Edema and cellular reaction produceunhealthy granulation tissue suscep-tible to bacterial invasion, and theconcomitant systemic response maybe severe and cause further debilita-tion in the burn patient.

Difficulties in obtaining adequatesupplies of cadaver skin led to asearch for substitute tissues. In 1957Rogers, Converse and Silvetti8 pro-posed concerted investigation into theuse of bovine embryo skin as a tem-porary dressing for large skin wounds.Bromberg, Song and Mohn9 laterreported the results of their labo-ratory and clinical investigations withpigskin xenografts, which, because oftheir commercial availability, havebecome popular in many centres.

The use of human amniotic mem-brane as a temporary biologic dress-ing has been evaluated recently, bothexperimentally and clinically, byRobson and Krizek.'0 In a series of

50 rat burns infected with 108 Pseu-domonas aeruginosa organisms, thisdressing was shown to be 1000 timesmore effective than split-thicknesshuman skin grafts in decreasing bac-terial contamination. In another ex-perimental model human amnioticmembrane was found to be as effect-ive as split-thickness isograft skin butsuperior to split-thickness allograftand xenograft skin in decreasing bac-terial contamination of full-thicknessskin defects created on the backs ofrats.11 The usefulness of human am-niotic membrane in the managementof open wounds was further substan-tiated by Robson and associates12'13 ina study of 150 patients, and by Cob-cho and colleagues14 in their use ofthe amnion layer alone as a physiol-ogic wound dressing in 107 patientswith partial-thickness burns and split-thickness graft donor sites.We undertook the study described

below to evaluate the usefulness andversatility of human amniotic mem-brane as a temporary biologic dress-ing in a wide variety of common andchallenging clinical situations, andto determine an optimal protocol forits use.

Methods

Patients

included in the study were 120 pa-tients in need of temporary biologicdressings. Their wounds were mainlyfull-thickness defects of diverseorigin and certain partial-thicknessdefects. Accurate clinical and photo-graphic records were kept.

Material

Fresh amniotic membranes wereobtained at the time of delivery fromwomen who were seronegative forsyphilis and had no history of prema-ture rupture of the membranes or en-dometritis. Meconium-stained orfoul-smelling membranes were dis-carded. With aseptic technique, mem-branes were removed from the pla-centa, not separated into amnion andchorion, and washed four times withsterile normal saline, once with0.025% sodium hypochborite solu-tion, then four times with normal

CMA JOURNAL/MAY 20, 1978/VOL. 118 1237

N..ofTyp. of wounits ptlntaUlurs

Nonhealing or poorly healingwounds 10

Burns 30Traumatic ioft-tlssuo wounds 7

FIG. lA-Chronic venous stasis ulcer. FIG. 2A-Pyoderma gangrenosum of perineoscrotal area;deep, burrowing ulcers with necrotic base and underminededges with black, "lifeless" appearance; anal stump evident.

FIG. lB-Human amniotic membrane applied to ulcer. FIG. 2B-After 6 weeks of application of human amnioticmembrane, undermined edges filled in, new epithelium atperiphery, and significant healing and wound contraction.

FIG. iC-Ulcer completely healed in 3 weeks. FIG. 3-Major full-thickness burn wound after separationof eschar; large membranes used to advantage.

CMA JOURNAL/MAY 20, 1978/VOL. 118 1239

3M Center, St. Paul, Minn.) and was

uniformly successful.

Nonhealing or poorly healing wounds

In 10 patients with nonhealing orpoorly healing wounds of diverseorigin human amniotic membranewas applied to stimulate healing andgranulation tissue formation. Most ofthese wounds had failed to respondto routine wound care and systemicsupport. The change in wound ap-pearance following application of themembranes was often striking, as inthe following cases:

Case 3: A 45-year-old man under-went total proctocolectomy for Crohn'sdisease. Pyoderma gangrenosum of theperineum developed thereafter, withsloughing and ulceration of almost theentire perineoscrotal area, which wascompletely resistant to all forms oftreatment for 18 months. Frequentdressings and sitz baths necessitatednarcotic analgesia. The wound prior tothe application of human amnioticmembrane is shown in Fig. 2A. Steroidsand azathioprine were being admin-istered for control of the Crohn'sdisease.

Pain was relieved when applicationof human amniotic membrane was be-gun. Every 48 hours the membrane wasremoved in a sitz bath and anotherapplied. No d.bridement or other formof wound care was used. Within 3weeks there was a remarkable trans-formation in appearance of the wound:the deeply undermined edges had filledin, epithelial ingrowth from the peri-phery was progressing rapidly, and theulcer base was replaced with healthy,bright-red granulation tissue. By 6weeks more than two thirds of the ul-ceration had healed and wound con-traction and epithelialization werestriking (Fig. 2B). Fatal cerebral hem-orrhage interrupted this progression ofevents, but the near-total healing ev-idenced prior to death was striking.

Case 4: In a 58-year-old man achylous fistula developed after pharyn-golaryngectomy and radical neck dis-section for recurrent hypopharyngealradiation therapy. A large area of tissueadjacent to the tracheostoma brokedown, with deep undermining of thewound edges, exposing the commoncarotid artery. After 4 weeks of applica-tion of routine dressings (sodium hypo-chlorite 1:20) 'minimal healing was ev-ident. Human amniotic membrane wasapplied directly to the exposed carotidartery and remaining wound surfaceand tucked under the deeply under-mined wound edges. Over the next 4weeks healthy granulation tissue filledthe wound, obliterating the undermined

edges and providing almost completecoverage of the exposed carotid artery.This allowed successful closure of thedefect with a deltopectoral flap.

In two cases human amnioticmembrane was applied directly tobone:

Case 5: Following aortocoronary by-pass grafting, postoperative sternal de-hiscence occurred in a 61-year-old man.The wound was resutured, but 2 dayslater dehiscence recurred, the wiresutures tearing through friable boneedges. Human amniotic membrane wasapplied to this deep wound, directlycovering the pericardium and the twolateral edges of the sternum. Frequentdressing changes were initially needed,but after 3 weeks 'healthy granulationtissue covered the pericardium andsternal surfaces, *and delayed woundclosure was performed.

Case 6: In a 50-year-old man a dis-tal tibial fracture remained ununiteddespite two attempts at open reductionand bone grafting, and osteomyelitisdeveloped at the fracture site. Follow-ing curettage and saucerization of thearea human amniotic membrane wasapplied directly to the bony cavity andadjacent exposed tendon. Healthygranulation tissue began to cover areasof exposed bone. The many remainingislands of pearly, avascular bone wereremoved on the ward and human am-niotic membrane was reapplied tohealthy, bleeding bone. Four weekslater, prior to coverage with a cross-legflap, the entire bony cavity and ex-posed tendon were covered withhealthy, bright-red granulation tissue.Because the exact extent of devitalizedbone was accurately determined, man-agement was facilitated.

Burns

Ten patients with full-thickness ordeep partial-thickness burns weretreated with human amniotic mem-brane. In full-thickness burns, oncethe eschar had been removed themembrane was applied to providecoverage and to promote the growthof healthy granulation issue prior toautografting (Fig. 3). Areas of thewound not ready for grafting (asshown by failure of the membrane totake) were prepared with frequentmembrane changes until take was ev-ident. Granulation tissue in the areasready for grafting was kept healthyuntil the entire wound was ready forgrafting. D.bridement of the burnsurface by frequent changes of mem-brane decreased the number of graft-ing procedures necessary to close thewound. With massive burns and lim-

ited autograft supply the membranecovered the wound while donor siteshealed. Membrane dressings reducedpain significantly, permitting earlymobilization, especially with burns ofthe hand.

Certain deep partial-thicknessburns covered with human amnioticmembrane after separation of theeschar showed accelerated healing ofthe remaining dermal elements. Coa-lescing epithelial islands were seenbeneath the membrane, which separ-ated spontaneously when epitheliali-zation of the underlying wound wascomplete. Healthy, pliable, normalskin, without hypertrophic scar, wasproduced. Human amniotic mem-brane was not used in the initial treat-ment of partial-thickness burns sincethermal injury often results in awound with patchy areas of partial-and full-thickness loss.

Traumatic soft-tissue wounds

In seven patients who had sufferedsevere soft-tissue and bony traumahuman amniotic membrane was usedas the immediate cover for contamin-ated wounds to protect exposed bone,nerves, tendons and vessels, and tomaintain tissue viability until defini-tive closure was possible. In woundsin which the tissue viability was ques-tionable the membranes were used todelineate areas of dead tissue andthus permit accurate d6bridement.

Discussion

Human amniotic membrane hasbeen used successfully as a temporarybiologic dressing in diverse clinicalsituations. Histologically the mem-branes consist of two loosely con-nected tissues, amnion and chorion.The amnion, or inner layer, is derivedfrom the epiblast and is continuouswith the embryonic ectoderm.'5 Theinner surface is composed of cuboidalor flattened epithelial cells; the outersurface is covered with mesenchymalconnective tissue. The chorion has amesenchymal component in contactwith the amnion, and an externalectoderm composed of transitionalepithelium. Pigeon18 has stated thatsince amniotic membrane is formedby fetal ectoderm it is really an ex-tension of the infant's skin. Lister17found ultrastructural and functionalsimilarities between fetal skin andamnion and chorion. Hence humanamniotic membrane can- be consi-dered analogous to fetal skin allo-

1240 CMA JOURNAL/MAY 20, 1978/VOL. 118

graft. This may account for certainof its beneficial effects when usedas a wound dressing.

In treating this series of patientswe made no attempt to separate themembrane into its two layers sincethe thicker two-layered membraneprovided a more satisfactory tem-porary wound cover; no disintegra-tion occurred within 48 hours whenadherence of the membrane wasmaintained. Douglas18 demonstratedinitial neovascularization of chorionapplied to experimental wounds, andRobson and Krizek13 showed de-creased bacterial growth when a tem-porary biologic dressing took initiallyon a granulating site. Therefore weapplied the chorion to the wound sur-face of all full-thickness wounds. Co-locho and colleagues14 showed con-clusively that no vascularization oc-curs when the amnion is applied tothe wound. Therefore in partial-thickness defects, for which vascular-ization is not desirable, we placed theamnion against the wound surface.This provided wound coverage, andthe membrane dessicated spontane-ously when epithelialization was com-plete.

All biologic dressings currentlyused (cadaver skin allograft, pigskinxenograft and human amniotic mem-brane) serve specific functions:* Reduction of bacterial conta-

mination and prevention of furthercontamination.* Reduction of fluid, protein,

heat and energy loss.* Reduction of pain.* Promotion of healing.* Protection of underlying struc-

tures.* Increase in mobility.* Prediction of tissue viability

when such is initially questionable.* Preparation of full-thickness

defects and recipient sites for auto-grafting or delayed closure.* Psychologic improvement in

the patient.Cadaver skin allograft and pigskinxenograft have certain disadvantagescompared with human amnioticmembrane. Cadaver skin is difficultto obtain; legal problems and the ex-clusion of cadavers with a history ofmalignant disease, hepatitis or syphi-lis are further difficulties. Personnelmust be available at all times to pro-cure the skin in a sterile manner,usually in the operating room. Bax-ter19 estimated that the cost of har-

vesting the skin of one cadaver was$225 and that it required, on theaverage, 6 hours of physicians' time.Pigskin is commercially available butcosts approximately $280/in1. Woodand Hale20 have estimated the costof pigskin dressings in an adult withburns of 44% of his body surfaceto be $219/d. Both allograft andxenograft skin dressings are limitedin size and shape. Human amnioticmembrane is readily available andfreely obtainable, and may be large.One of the main benefits of wound

coverage with a biologic dressing isprevention of contamination and re-duction of infection. Eade" showedthat in burns, granulation tissue isalways heavily contaminated Withorganisms; coverage with fresh viableor preserved nonviable autograft orallograft permitted granulation tissueto destroy contained organisms rapid-ly. Morris, Bondoc and BurkeU be-lieved that this antibacterial effect layin the intimate closure of the openwound provided by the biologicdressing, which prevented furtherbacterial contamination and allowedthe host's defence mechanisms todeal with the infection effectively.Larson.' found that the decrease inthe count of bacteria paralleled therapid increase in the count of leuko-cytes beneath the graft. This wasconfirmed by Saymen and col-leagues,'. who showed that in un-covered infected rat wounds leuko-cytes tended to migrate from themuscle surface to the base, and thatthis migration reversed after the ap-plication of allograft skin. They sug-gested that this alteration in cell mi-gration might modify leukocyte func-.ion and result in greater bactericidalactivity. The reduction in bacterialcontamination and reversal of leuko-cyte migration did not occur in theabsence of wound coverage. Burlesonand Eiseman.' found that the anti-bacterial effect of biologic dressingswas related to the adherence to theunderlying wound bed. "Skin thatstuck sterilized." They demonstratedwith pigskin that this adherence wasrelated to a fibrin-elastin biologicbond.

Experimentally human amnioticmembrane has proven equal to auto-graft skin and superior to allograftand xenograft skin in decreasing bac-terial counts in open granulatingwounds.10'11 Clinically the ability ofhuman amniotic membrane to de-

crease bacterial counts was equal tothat of allograft skin and superior tothat of xenograft skin, probably be-cause of the greater pliability andadherence of human amniotic mem-brane with intimate wound closureand obliteration of dead "Inaddition, the mechanical d.bridementthat accompanies frequent membranechanges allows host resistance factorsin the granulating bed to function atpeak efficiency. The initial take ofmembrane to the granulating bedprobably contributes to this salutaryeffect since the lack of effectivenessof xenograft skin in decreasing bac-terial counts has been related to itsinability to take initially on a granu-lating wound surface.19 The recentreduction in the neomycin content ofcommercial pigskin has further de-creased this dressing's effective-ness.."7

Other mechanisms have been pos-tulated for the antibacterial propertiesof human amniotic membrane. Lyso-zyme, a bactericidal protein, is pre-sent in high concentration in humanamniotic membrane, and progeste-rone, which is bacteriostatic for cer-tain gram-positive organisms, is alsopresent.28 Allantoin is present as well(C.W. Brigden, personal communica-tion, 1977). Indeed, the beneficialeffect of maggots on contaminatedwounds has been considered to bedue to their excretion of allantoin.

Skin graft survival and successfulclosure of a contaminated wound bysuture or skin graft have been shownto correlate accurately with a woundconcentration of 10' or fewer bac-teria per gram of tissue, except for/3-hemolytic streptococci, whose con-centration must be lower for success-ful grafting or wound closure.19'29Allograft take has been found to cor-relate accurately with a wound con-centration of 10' bacteria per gramof tissue, and this forms the basis ofthe allograft test. In this way theprevious subjective evaluation ofwound readiness for grafting or de-layed closure has been replaced byobjective allograft testing of thewound surface. Take of human am-niotic membrane to the wound sur-face invariably predicts successfulautograft take or wound closure. Thishas particular application in the man-agement of contaminated, infectedand burn wounds and chronic skinulcers. Delineation of areas of deadtissue to limit the extent of d6bride-

CMA JOURNAL/MAY 20, 1978/VOL. 118 1245

ment is especially important in handand face injuries, wringer injuriesand wounds caused by gunshot orother high-velocity projectiles, inwhich excessive d6bridement canseverely restrict function and resultin cosmetic deficiency.30

Promotion of healing followingwound coverage with a biologicdressing has been reported by manyauthors.31-34 In rabbits, wound heal-ing was accelerated after the applica-tion of human amniotic membrane:the repair process started earlier, themigration of fibroblasts and the de-velopment of collagen were hastenedduring the first 6 to 8 days of heal-ing, and epithelialization occurredsooner. . In addition, allograft skinseems to have an organizational ef-fect on the healing wound:22 second-degree burns not covered by allograftshowed edema and inflammation inthe dermis, with disorganization ofnormal maturation and loss of cellpolarity, whereas in wounds coveredby allograft the epidermis showednormal structure with a recognizablebasal layer and a normal-appearingcollagen layer in the dermis.36 Hyper-trophic scarring and keloid formationseem to be prevented in this way.We did not use human amniotic

membrane for split-thickness skingraft donor sites, which heal rapidlywith routinely used dressings andrarely pose a problem clinically.

Conclusions

Human amniotic membrane wasused successfully as a temporary bio-logic dressing for various wounds in120 patients. The membrane is easilyobtained, at little or no cost. It pro-vides excellent wound coverage andhas distinct advantages comparedwith other biologic dressings.

References

1. GIRDNER JH: Skin grafting with graftstaken from the dead subject. Med Rec20: 119, 1881

2. REVERDIN JL: Greffe .pidermique.Bull Soc Imp Chir Paris 10: 511, 1869

3. LEE EW: Zoografting in a burn case.Boston Med Surg J 103: 260, 1880

4. DAVIS JS: Skin transplantation. Witha review of 550 cases at the JohnsHopkins Hospital. Johns HopkinsHosp Rep 15: 307, 1910

5. SABELLA N: Use of fetal membranesin skin grafting. Med Rec NY 83: 478,1913

6. Dooo G: Survival and utilization ofcadaver skin: preliminary note. PlastReconstr Surg 10: 10, 1952

7. BROwN JB, FRYER MP, RANDALL P, etal: Postmortem homografts as "bio-logical dressings" for extensive burnsand denuded areas; immediate andpreserved homografts as life-savingprocedures. Ann Surg 138: 618, 1953

8. ROGERS BO, CONVERSE JM, SILvETTIAN: Preliminary clinical studies onbovine embryo skin grafts. TransplantBull 4: 24, 1957

9. BROMBERG BE, SONG IC, MOHN MP:The use of pig skin as a temporarybiological dressing. Plast ReconstrSurg 36: 80, 1965

10. ROBSON MC, KRIZEK TJ: The effectof human amniotic membranes on thebacterial population of infected ratburns. Ann Surg 177: 144, 1973

11. RoBSoN MC, SAMBURG JL, KRIZEK TJ:Quantitative comparison of biologicaldressings. J Surg Res 14: 431, 1973

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13. RonsoN MC, KRIZEK TJ: Clinical ex-periences with amniotic membranes asa temporary biologic dressing. ConnMed 38: 449, 1974

14. CoLocHo G, GRAHAM WP III, GREENEAE, et al: Human amniotic membraneas a physiologic wound dressing. ArchSurg 109: 370, 1974

15. BAILEY FR, MILLER AM: Textbook otEmbryology, 2nd ed, Wood, NewYork, 1911

16. PIGEON J: Treatment of second-degreeburns with amniotic membranes. CanMed Assoc J 83: 844, 1960

17. LISTER UM: Ultrastructure of the hu-man amnion, chorion and fetal skin.J Obstet Gynaecol Br Commonw 75:327, 1968

18. DOUGLAS B: Homografts of fetalmembranes as a covering for largewounds - especially those fromburns; experimental and clinical study(preliminary report). J Tenn Med As-Soc 45: 230, 1952

19. BAXTER CR: Homografts and hetero-grafts as a biological dressing in thetreatment of thermal injury. Presentedat the first annual congress of theSociety of German Plastic Surgeons,Munich, Sept 28, 1970

20. WOOD M, HALE HW JR: The use ofpigskin in the treatment of thermalburns. Am J Surg 124: 720, 1972

21. EADE GG: The relationship betweengranulation tissue, bacteria, and skingrafts in burned patients. Plast Re-constr Surg 22: 42, 1958

22. MORRIS PJ, BoNnoc C, BURKE JF:The use of frequently changed skinallografts to promote healing in thenon healing infected ulcer. Surgery60: 13, 1966

23. LARSON D: in discussion, ibid24. SAYMEN DG, NATHAN P, HOLDER IA,

et al: Control of surface wound in-

fection: skin versus synthetic grafts.Appi Environ Microbiol 25: 921, 1973

25. BURLESON R, EISEMAN B: Mechan-isms of antibacterial effect of biologicdressings. Ann Surg 177: 181, 1973

26. HABAL MB: On the cutaneous porcineheterograft (E). Plast Reconstr Surg57: 367, 1976

27. A short note on the physiologicresponse to the cutaneous xenograftas a biologic dressing (C). J Trauma14: 94, 1974

28. GALASK RP, SYNDER IS: Antimicrobialfactors in amniotic fluid. Am J ObstetGynecol 106: 59, 1970

29. RonsoN MC, HEGGERS JP: Surgicalinfection. II. The P-hemolytic strepto-coccus. J Surg Res 9: 289, 1969

30. BURKE JF, BONDOC CC: A method ofsecondary closure of heavily conta-minated wounds providing "physio-logic primary closure". J Trauma 8:228, 1968

31. RonsoN MC, HEGGERS JP: Bacterialquantification of open wounds. MilitMed 134: 19, 1969

32. GILLMAN T, PENN J, BRONKS E, et al:Reactions of healing wounds andgranulation tissue in man to auto-thiersch, autodermal, and homodermalgrafts; with analysis of implications ofphenomena encountered for under-standing of behaviour of grafted tis-sue and genesis of scars, keloids, skincarcinomata, and other cutaneous le-sions. Br J Plast Surg 6:153, 1953

33. ZAROFF LI, MILLS W JR, DUCKETTJW JR, et al: Multiple uses of viablecutaneous homografts in the burnedpatient. Surgery 59: 368, 1966

34. O'NEILL JA JR, GROSFELD JL, BOLESET JR: The extended use of skinhomografts. Arch Surg 99: 263, 1969

35. BAPAT CV, Kom.u.. PM: Preliminaryreport on acceleration of wound heal-ing by amnion membrane graft. In-dian J Med Res 62: 1342, 1974

36. MILLER TA, SWITZER WE, FOLEY FD,et al: Early homograting of seconddegree bums. Plast Reconstr Surg 40117, 1967

BOOKScontinued from page 1235PROBLEM SOLVING IN IMMUNOHEMA-TOLOGY. Case Reports For PathologistsAnd Medical Technologists. Arthur Sim-mons. 204 pp. Illust. Year Book MedicalPublishers, Inc., Chicago, 1977. $15.35,spiral bound. ISBN 0-8151-7654-6

PROTEINS OF ANIMAL CELL PLASMAMEMBRANES. Vol. 1, 1977. D.F.H. Wal-lach. 154 pp. Eden Press Inc., Montreal,1977. $18. ISBN 0-88831-011-0RECENT ADVANCES IN CLINICAL BIO-CHEMISTRY. No. 1. Edited by D.G.M.M.Alberti. 298 pp. Illust. Churchill Living-stone, Edinburgh; Longman Canada Lim-ited, Don Mills, 1978. $41.60. ISBN 0-443-01590-2

continued on page 12541246 CMA JOURNAL/MAY 20, 1978/VOL. 118