CATABOLISM OF PLASMA-PROTEINS

131

regained in a few minutes. pain or restlessness.

There

was no

postoperative

I am greatly indebted to Dr. Russell M. Davies for his untiring help and guidance in the preparation of this paper, and to Mr. C. R. McLaughlin for his advice and valuable comments. Janssen Research Laboratories, Beerse, Belgium, supplied the R.4263 and R.4749,, and the investigation was supported in part by the East Grinstead

Anaesthesia Research Trust Fund. REFERENCES L. (1951) Anœthesia, 6, 20. Bromage, P. R. (1951) ibid. p. 26. De Castro, G., Mundeleer, P. (1962) in Proceedings of 1st European

Bilsland, W.

Congress of Anæsthesiology; Vienna. Enderby, G. E. H. (1958) Brit. med. Bull. 14, 49. Holloway, K. B., Holmes, F., Hider, C. F. (1961) Brit. J. Anœsth. 33, 648. Janssen, P. A. J. (1962a) Unpublished. — (1962b) in Proceedings of 1st European Congress of Anæsthesiology; Vienna.

Lancet

(1962) ii,

818.

Mason, A. A., Pelmore, J. F. (1953) Brit. med. J. i, 250. Murtagh, G. P. (1960) Anœsthesia, 15, 235. G. (1950) Proc. R. Soc. Med. 43, Organe, Saunders. J. W. (1952) Lancet. i. 1286.

185.

Addendum

An additional 9 cases of induced hypotension have been completed with good results in 8. Postoperative complications have been limited to vomiting in 2 patients.

CATABOLISM

OF PLASMA-PROTEINS

A. S. MCFARLANE M.A., M.B., B.Sc. Glasg. From the

Biophysics Division of the National Institute for Medical Research, London, N.W.7

EFFORTS in many laboratories to identify the site of catabolism of plasma-proteins have not been altogether successful. Cohen and Gordon (1958) claim that 15% of the total amount of albumin known from isotope studies to be catabolised per day is destroyed in the liver. Jeejeebhoy and Coghill (1961) and Tarver et al. (1961) hold that 50% or more is destroyed in the lumen of the gastrointestinal tract. But the possibility has not been excluded that much of it is diffusely catabolised-for example, in endothelium all over the body. The problem has more than academic interest since the interpretation of almost any kind of metabolic study of plasma-proteins is affected.

excretion-rate and plasma-decay-rate was accidental, and was due to iodide being produced by catabolism of denatured labelled albumin in sufficient amount to compensate for iodide retained in the body water.

To

hypothesis 1311 rabbit-albumin of high was prepared by methods already described (McFarlane 1956, 1958) and injected into a normal rabbit. After 2 days during which any denatured labelled protein could be expected to be selectively catabolised, 2 ml. of the plasma was transferred to another normal animal and daily urine radioactivities were test

specific

this

activity

measured in both animals. After division by corresponding mean total plasma activities on the same day these were plotted in the accompanying figure as plasma catabolic-rates. The lower curves show the daily measurements of the proportion of non-precipitable activity in the plasma obtained by trichloracetic-acid precipitation. These are readily converted to iodide activity in the total body water using a factor of 8 for the ratio of iodide in the body water to iodide in the plasma (Reeve and Roberts 1959a). When the daily increment or decrement in this activity was added to activity in the urine on the same day, the solid curves were obtained, the dotted curves being based on activities present only in the urine. It will be seen that with the original unscreened albumin more iodide was liberated in the first 2 days than corresponds to the steady rate of breakdown (22%) of plasma-albumin subsequently established, whereas with albumin screened for 2 days the rate was constant (17%) from the time of the second urine collection at 6 hours. The difference in the two rates is within the range of metabolic variation normally found in rabbits (Cohen et al. 1956). This evidence for a constant rate of intravascular

Recognising the deficiencies in our knowledge on this matter, measuring the fractional catabolic-rate of albumin in the whole animal with isotopes prefer to leave the matter there (Berson et al. 1953, Gitlin et al. 1958). To proceed further and to specify catabolism in g. per day requires a knowledge which is seldom available of the total albumin in the many workers after

body. Others have deduced evidence in favour of a site which is sufficiently close in a metabolic sense to the plasma to justify compounding the measured fractional catabolic-rate of protein in the plasma with the known mass of albumin in the plasma and, thus, to infer a mass catabolic-rate (Campbell et al. 1956, Reeve and Roberts 1959b, Cohen et al. 1961, Beeken et al. 1962). The evidence is based on the observation that the rate of excretion of radioactivity is the same as the rate of disappearance of iodine-labelled albumin from the plasma, but not from the whole body. This observation is not significantly affected by the fact that only 90 % of the excreted activity is in the form of iodide (Lewallen et al. 1959, Zizza et al. 1959) and that it is necessary to recognise a breakdown-products pool interposed between the plasma and urine (Reeve and Roberts 1959a). It has been impossible to establish this correlation, however, in the first 2 days of the experiment when much of the iodide liberated by catabolism accumulates in the body water. Also, normally in man after the 8th day the radioiodide excretionrate is approximately the same as that of the decay of total body activity (McFarlane 1957). The disturbing possibility exists that during this six-day interval the observed identity of

Plasma catabolic-rates and (lower curves) proportions of precipitable activity in plasma of two rabbits.

non-

received unscreened z1 rabbit-albumin. received same protein screened in A for 2 days. D indicates daily urine activities; E indicates daily urine activities and incremental iodide activities in body water. Both are divided by mean total plasma activities on the same day. A B

132

protein breakdown in the first 2 days is particularly convincing, since at this time albumin is passing rapidly into the extravascular space. The method of calculating the mass rate of albumin catabolism from plasma and urine activities and the total mass of albumin in the plasma appears therefore to be justified. Summary Radioactivity excreted in the urine of a rabbit injected with 131I-albumin which had been biologically screened for 2 days to remove traces of denatured protein was found to represent a constant fraction of the activity in the plasma at the same time, even in the first 2 days when plasma activities were declining rapidly. This is taken to indicate that catabolism of albumin occurs at a site which is in close metabolic relationship to the intravascular "

"

DrntMn REFERENCES

Beeken, W. L., Volwiler, W., Goldsworthy, P. D., Garby, L. E., Reynolds, W. E., Stogsdill, R., Stemler, R. S. (1962) J. clin. Invest. 41, 1312. Berson, S. A., Yalow, R. S., Schreiber, S. S., Post, J. (1953) ibid. 32, 746. Campbell, R. M., Cuthbertson, D. P., Matthews, C. M., McFarlane, A. S. (1956) Int. J. appl. Radiat. 1, 66. Cohen, S., Freeman, T., McFarlane, A. S. (1961) Clin. Sci. 20, 161. Gordon, A. H. (1958) Biochem. J. 70, 544. Holloway, R. C., Matthews, C., McFarlane, A. S. (1956) ibid. 62, 143. Gitlin, D., Cravioto, J., Frenk, S., Montano, E. L., Galvan, R. R., Gomez, F., Janeway, C. A. (1958) J. clin. Invest. 37, 682. Jeejeebhoy, K. N., Coghill, N. F. (1961) Gut, 2, 123. Lewallen, C. G., Berman, M., Rall, J. E. (1959) J. clin. Invest. 38, 66. McFarlane, A. S. (1956) Biochem. J. 62, 135. (1957) Ann. N.Y. Acad. Sci. 70, 19. (1958) Nature, Lond. 182, 53. Reeve, E. B., Roberts, J. E. (1959a) J. gen. Physiol. 43, 415. (1959b) ibid. p. 445. Tarver, H., Armstrong, F. B., Debro, J. R., Margen, S. (1961) Ann. N.Y. Acad. Sci. 94, 23. Zizza, F., Campbell, T. J., Reeve, E. B. (1959) J. gen. Physiol. 43, 397. —

—

—

—

—

—

POSTOPERATIVE SEPSIS IN A SMALL SURGICAL UNIT M.B.

A. LITTON Glasg., F.R.C.S., F.R.C.S.E.

In all cases, preoperative skin preparation of the operation site was carried out according to the established unit practice: that is, on the day before operation, after the patient had bathed the skin was shaved and then painted with an 0-1% solution of merthiolate; and the treated area was covered with a sterile towel. The following morning the skin of the operation site was prepared again in the same way, the operation was performed in the afternoon. The sterile towelling was removed in the theatre immediately before the final skin preparation, at the beginning of the operation. At the start of each operating session, the following samples were obtained: nasal swab from the surgeon, his assistant, and the theatre sister; and nasal swab and swab of the operation site from the patient. The swab of the operation site was taken after the preparation towelling had been removed, and before the final preparation of the skin in theatre. Preoperatively, the staff prepared their hands, using a 3% hexochlorophene mixture (Lowbury and Lilly 1960). At the end of each operation a sample was taken from the depths of the wound, and when the incision had been closed a further sample was taken from the wound surface. When the operating session was completed and the gloves were being removed, swabs were taken from the palmar surfaces of the hands of the surgeon, his assistant, and the theatre sister. All samples were obtained by wiping the relevant area with a swab-stick moistened in sterile nutrient broth. When the last sample from the wound surface had been taken, the wound was dressed with a gauze pad and sealed with elastic adhesive dressing; and, unless drainage had been carried out, the dressing was not disturbed until the sutures were removed, when a further swab of the wound surface was taken. At this time a clinical assessment as to whether the wound was clean or septic was made; and, since the theatre dressings had remained undisturbed, cross-infection in the wards was considered unlikely (Gillespie et al. 1961). A wound was regarded as septic clinically if local redness and pus were

present.

samples taken during the survey were investigated for pathogenic staphylococci, and for their pattern of antibiotic sensitivity and phage-type. The production of coagulase by a staphylococcus was held to indicate pathogenicity. All

any

SENIOR SURGICAL REGISTRAR

R. D. C. SINCLAIR

Results

M.B. Edin.

growth of the theatre; pathogenic staphylococci those of the other surgeon were negative on every occasion. Owing to rotation of personnel, seven different assistants took part in the survey. Three of the assistants had consistently negative swabs; one had a random positive culture for pathogenic staphylococci; and the remainder had almost consistently positive samples. The theatre sister had positive nasal swabs on thirty-three out of a total of forty visits. On six visits to theatre, all three of the operating team were nasal carriers of pathogenic staphylococci. On thirteen occasions two of the team were positive. On nineteen occasions one of the team was

SENIOR HOUSE-OFFICER IN PATHOLOGY

The nasal swab of

*

SOUTHERN GENERAL HOSPITAL, GLASGOW

THE problem of staphylococcal infection of surgical wounds is increasingly important. Two main reservoirs from which wounds become infected with staphylococci are apparently the noses of theatre personnel and of the patient himself (Williams 1959, McNeill et al. 1961). We have attempted to assess these factors in a group of patients who were subjected to elective surgery in a small unit where many of the suspected causes of wound infection could be controlled or eliminated. Methods The survey was carried out in a self-contained, thirty-bed hospital which catered solely for elective surgical cases. The building was previously a cottage hospital but is now attached to the surgical unit of a large general hospital, though still functioning as a separate unit. Patient accommodation consisted of two small wards and three side-rooms. The theatre was used twice weekly for elective operating sessions. The group of patients studied consisted of a hundred consecutive cases admitted from the waiting-list, those cases requiring anorectal surgical procedures having been excluded; these were operated or. at the end of the sessions. The biweekly operating sessions were carried out by two surgeons working in rotation. In view of the small size of the hospital, the limited number of staff involved, and the absence of emergency and septic cases, some of the factors which have been claimed to be important in the causation of infection, were eliminated. * Present appointment: lecturer in bacteriology, University of Edinburgh.

one

surgeon

at every

yielded

visit

a

to

positive, and

on only two occasions were no

nasal

carriers present in the

operating team (fig. 1). On no occasion was a

positivee

sample Fig. 1-Number of nasal carriers present in a series of 40 operating sessions: surgical team and patients shown separately.

ob-

tained from the hands of the operating teams in res-