208

shown in table n. The anti-staphylococcal activity of thecephalosporins may explain their usefulness in preventingStaph. aureus wound infections.4 Although cephalosporinswere in general less effective against gram-negative organismsthan the aminoglycosides, there was no wound infection in anypatient pretreated with cephalosporins. Gentamicin seems tobe a logical alternative to the cephalosporins for biliary-tractprophylaxis since both Staph. aureus and E., coli are com-

pletely inhibited by this antibiotic. Gentamicin may be able toprevent infection after biliary-tract surgery because it pene-trates gallbladder-wall tissue.’A single, parenteral, preoperative dose of an antibiotic is

thus the optimal prophylactic regimen for preventing woundinfections associated with cholecystectomy.6 The prophylacticregimen need not be continued for more than 24 h after sur-gery since wound infections originate during the operation.’The choice of an antibiotic for prophylaxis should take intoaccount the drug’s in-vivo or in-vitro activity against the pre-sumed pathogens and the drug should be able to penetrate thetarget tissues-e.g., the wound or gallbladder wall-in ade-quate concentration for the duration of the operation.

Cephalosporins are a logical choice in biliary-tract surgerybecause they are active against Staph. aureus and most col-iform bacteria. Ampicillin has only limited activity againstthese organisms but is indicated when the enterococcus is thepresumed pathogen.8 Gentamicin is more consistently activeagainst the usual coliform bacteria than are the cephalosporinsand, in addition, is active against staphylococci;9 it is thus areasonable alternative to the cephalosporins for the prophy-laxis of patients undergoing cholecystectomy. 10Division of Infectious Diseases

and Departments of Internal Medicineand Surgery,

Hartford Hospital,Hartford, Connecticut 06115, U.S.A.

BURKE A. CUNHALUDWIG J. PYRTEKRICHARD QUINTILIANI

LABORATORY-PREPARED REAGENTS ORCOMMERCIAL KITS

SiR,-Mr Richardson’s article’ is of interest since it is nowfashionable to explore less costly (or better) methods of acquir-ing much-used hospital laboratory reagents. However, thereare dangers in making unrealistic claims for economy in home-made products. For example, in ascribing costs to preparationof "in house" reagents Richardson made no allowance forfixed overheads such as rent, heat, light, and power. Capitalinvestment and the need for eventual replacement of equip-ment should also be allowed for.The Protein Fractionation Centre has been collaborating

with the biochemistry department of the Victoria InfirmaryGlasgow to produce a bovine serum for clinical control pur-poses, and there is little doubt that products made in this wayare cheaper than the commercial equivalent. Producing for a"home" market makes it possible to adjust constituents to userspecification and to prepare special batches for specific pur-poses.The centre operates in five divisions of which one is the pro-

duction division. Thus the cost element for staffing must allowfor labour, supervision, and support services such as engineer-ing, quality control, and administration. It seems probable thatin Richardson’s analysis the margin of 32%, for the most profi-table comparison between "in house" and "bought-in" kits at

4. Nightingale, C. H., Greene, D. S., Quintiliani, R. J. pharm. Sci. 1975, 64,1899.

5. Cunha, B. A., Quintiliani, R. Abstr. Soc. Microbiol. 1977, 77, 15.6. Strachan, C. J. L. and others. Br. med. J. 1977, i, 1254.7. Burke, J. F. Surgery, 1961, 1961, 50, 161.8. Pyrtek, L. J., Bartus, S. A. Surgery Gynec. Obstet. 1967, 125, 101.9. Richards, F., McCall, C., Cox, C. J. Am. med. Ass. 1971, 215, 1297.

10. Cunha, B. A., Klimek, J. J., Quintiliani, R. Curr. Ther. Res. 1976, 19, 529.1. Richardson, R. W. Lancet, 1977, ii, 1273.

the 200-per-day level for serum-aspartate-transaminase, is notsufficient to cover all overheads.

This criticism is not intended to be destructive of the basicthesis that the N.H.S. should prepare in-house reagents. TheN.H.S. has vast resources which could support projects of thistype; however, at this stage all costing should be very conser-vative. There is obvious merit in being able to claim that in-house preparation is less costly, but in the initial stages it ismore valuable to discover that it is not more costly than com-mercial sources and, if possible, of better quality.

Economic viability tends to be a matter of scale and, whilstquestioning the validity of the conclusion drawn by Richard-son, we have no doubt that, on a larger scale, in-house prep-aration could be very profitable. Perhaps several laboratoriescould combine to produce a range of reagents, each at a scaleto satisfy a regional need. Basically, that is what the Scottishtrial represents, except that the inclusion of the Protein Frac-tionation Centre in the project injects non-commercial, N.H.S.financed industrial processing technology and skills for operat-ing at scales well beyond the scope of almost all hospital labor-atories. Single-source reagents or quality-control materialmust be independently tested by centres which employ primarymethods of standardisation before they are released.

Protein Fractionation Centre,Scottish National Blood Transfusion Service,Edinburgh EH17 7QT JOHN G. WATT

Biochemistry Department,Victoria Infirmary,Glasgow G42 9TY ANDREW P. KENNY

HEPARIN-INDUCED DECREASE IN CIRCULATINGANTITHROMBIN III

SIR,-Marciniak and Gockerman reported that heparin,when present in the blood of patients for prolonged periods,reduced circulating antithrombin-III (A.T. III) levels.l How-

ever, they do not indicate the duration of heparin treatment inthe twenty-two patients in whom A.T. m levels were being mea-sured. It would seem that in five patients heparin was con-tinued for 5-6 days. A.T. III, measured as antigen and as func-tional binding capacity, fell for 3-4 days and then levelled out.What would happen to the A.T. in if heparin were continuedfor longer?

In this hospital many patients with postoperative deepvenous thrombosis are given intravenous heparin by constantinfusion for much longer than the traditional 7-10 days, oftenuntil the maximum clinical improvement has been achieved.Control is monitored by twice-daily thrombin-times. Heparinrequirements-sufficient to maintain the thrombin-time in the"therapeutic range" of 25-55 s (giving a ratio of 2:4. 5)--oftenincrease for several days, usually less than 7, and after a steadyperiod of a few more days may then decrease. The require-ments then become steady, the dose varying from patient topatient. I have always assumed that heparin requirements areinversely proportional to A.T. III, though A.T. III has not beenmeasured sequentially. My observation would be explained bya fall in A.T. 111 in the early days of heparin therapy, as

reported by Marciniak and Gockerman, followed by a rise andthen a steady state.One patient with iliofemoral deep venous thrombosis had

increasing heparin requirements through her first week ontreatment. Intravenous heparin was then stopped and she hada clinical extension of her thrombosis. Heparin was re-intro-duced and her requirements fell steadily over the next week,when she was able to come off intravenous treatment withoutfurther trouble.The implications of these observations are clearly important

as they may well have a bearing on the ideal time for heparin-isation of any particular patient, at present an unknown quan-

1. Marciniak, E., Gockerman, J. P. Lancet, 1977, ii, 581.