virus vaccine and antilymphocyte serum

1
980 gastric ulcer or Menetrier’s disease may make radiological assessment of acid secretion unreliable in individual patients. We accept that hookworm infestation may well be another such condition, but fortunatelv it is not common in our Dractice. G. P. BURNS J. W. LAWS. Departments of Surgery and Radiodiagnosis, Postgraduate Medical School, Ducane Road, London W.12. EFFECTS OF PARTIAL GASTRECTOMY G. R. THOMPSON G. NEALE J. M. WATTS C. C. BOOTH. Postgraduate Medical School, Ducane Road, London W.12. SIR,-We thank Dr. Morgan and his colleagues for their comments (April 2) and agree that our post-gastrectomy patients were a selected sample and that those studied in detail were few in number. We continue to differ, however, about the significance of a raised serum-alkaline phosphatase (S.A.P.) after partial gastrectomy. The association of a raised S.A.P., without other obvious cause, with subnormal levels of vitamin- D-like activity in the plasma, skeletal rarefaction, and an abnormal calcium infusion test, even in the presence of an apparently normal bone-biopsy, suggests to us that the bio- chemical abnormality is due to vitamin-D deficiency, particu- larly when there is response to oral or intravenous, rather than intramuscular, vitamin D. This is the situation that we referred to as " subclinical osteomalacia ". Dr. Morgan and his colleagues may well be right in suggest- ing that we have been missing significant microscopic changes in the past. But Dr. Ph. Bordier and Dr. H. Matrajt, of the Centre du Metabolisme Phosphocalcique, Paris, have examined a bone-biopsy from one of our patients with subclinical osteo- malacia ; they report that the undecalcified sections of bone, stained with ’ Solochrome Cyanine R’, were normal on all the criteria mentioned by Dr. Morgan and his colleagues, although this patient had shown a biochemical response to vitamin D. Dr. Bordier and Dr. Matrajt did notice, however: that in certain other respects the biopsy was not entirely normal. These abnormalities are being investigated further and will be reported as soon as their significance has been assessed. CONTAMINATED IRRIGATING FLUID SIR,-Dr. Last and his colleagues (Jan. 8) describe bac- teraemia after urological instrumentation, and Dr. Mitchell and his colleagues (April 9) report urinary-tract infections caused by contaminated irrigating fluid. In a study of postoperative urinary infection at this hospital an organism was found in the urine of 30 gynoccological patients during bladder drainage by indwelling catheter. The bacterium, which was oxidase-positive, was most nearly identified as Alcaligenes fcecalis, and like the commonest isolate of Dr. Last and his colleagues it seemed to be a " water organism ". In most patients these organisms were found intermittently and usually in small numbers, but in a few instances repeated cultures showed a heavy growth sometimes with pyuria. The organisms, like those found by Dr. Last and his colleagues, were presumably of low pathogenicity, but perhaps capable of infecting subjects particularly liable to urinary-tract infection. Investigations showed that the spigots used for closure of the catheters were heavily contaminated with this " water organism" as was the jar of 0-1% chlorhexidine solution in which the spigots were stored after disinfection by boiling. When artery forceps were used in place of spigots for the closure of drainage tubing this organism was no longer found in urine specimens. Laboratory tests showed that the organism would multiply from a small inoculum in 0- 1 % chlorhexidine in distilled water. It is, however, no new observation that there are bacteria capable of surviving in chlorhexidine solutions; the manufact- 1. Matrajt, H., Hioco, D. Stain Technol. 1966, 41, 97. urers themselves have drawn attention to this. Corks provide a well-known source of bacteria; I have isolated Pseudomonas pyocyanea (Ps. aeruginosa), and organisms of either the mima or the alkaligenes group from a high proportion of corks in stock- bottles of distilled water and chlorhexidine. Anderson et al.l have shown that even when bacteria are susceptible to the disinfectant transitory contamination may occur. The use of screw-caps and glass or plastic stoppers avoids this hazard, but if chlorhexidine solutions are to be introduced into body cavities-e.g., the bladder-they should be first heat-sterilised. These findings provide yet another illustration of the difficulties of attempting to sterilise or to maintain the sterility of surgical equipment by immersion in disinfectant solution. Disposable spigots for drainage tubes and catheters may now be obtained, packed singly, and sterilised by y-irradiation. C. DULAKE ELIZABETH KIDD. King’s College Hospital, London S.E.5. VIRUS VACCINE AND ANTILYMPHOCYTE SERUM M. F. A. WOODRUFF. Department of Surgical Science, Medical School, University of Edinburgh. SIR,-Reports from this department that the survival of skin homografts is greatly prolonged in rats treated with heterospecific antilymphocytic serum (A.L.S.) appear to have stimulated considerable interest in this material. More recent experiments in which dogs bearing kidney homotransplants were treated with horse-antidog-A.L.s. have proved equally encouraging so far as transplant survival is concerned. Two of eight treated dogs, however, died of distemper, although they had been actively immunised by a commercial vaccine containing live attenuated distemper virus, and it seems just possible that the infection was due to activation of virus persisting in these animals. The experiments are being fully reported.3 Since we and, we believe, others have prepared horse-antihuman-A.L.s. for possible therapeutic use in renal transplant recipients and patients with autoimmune disease, however, it seems desirable to draw attention to the risk of viral infection which the use of this serum may entail. In sounding this note of caution I am not suggesting that the danger is insurmountable, or indeed that it should necessarily prohibit cautious clinical trial at the present time. There are, for example, patients who continue to reject a renal transplant despite all other forms of treatment, and for whom no place can be found in a chronic dialysis programme, in whom the use of A.L.S. might be justified. But pending further investiga- tion it would certainly seem unwise to administer A.L.S. to any patient who has been inoculated with living poliomyelitis vaccine. RESPONSE TO PHYTOHÆMAGGLUTININ SIR,-Some confusion may arise from Dr. Elves’ remarks in his letter (April 16) on the role of serum-factors in cultures of stimulated lymphocytes. His findings suggest that plasma- factors are of little importance in chronic lymphocytic leukaemia, and that the main variable is the lymphocyte itself. In making this point Dr. Elves gives the impression that the source of human serum used for culture is immaterial. That there are important serum and plasma factors in normal and pathological human blood-samples can be shown,4 as well as in blood from other species. The work of Dr. Elves and his colleagues (March 26) would itself give some support to this suggestion. Using the mixed lymphocyte reaction in plasma from urxmic patients before and after dialysis they found improved trans- 1. Anderson, K., Keynes, R. Br. med. J. 1958, ii, 274. 2. Woodruff, M. F. A., Anderson, N. F. Nature, Lond. 1963, 200, 702; Ann. N.Y. Acad. Sci. 1964, 120, 119. 3. Abaza, H. M., Nolan, B., Watt, J. G., Woodruff, M. F. A. Unpublished; Woodruff, M. F. A., Anderson, N. F., Abaza, H. M. in Lymphocyte Symposium (edited by J. M. Yoffey). London (in the press). 4. Holt, P. J. L., Ling, N. R., Stanworth, D. R. Immunochemistry (in the press). 5. Holt, P. J. L., Ling, N. R. Unpublished. 6. Metcalf, W. K. Expl. Cell. Res. 1965, 40, 490.

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980

gastric ulcer or Menetrier’s disease may make radiologicalassessment of acid secretion unreliable in individual patients.We accept that hookworm infestation may well be another suchcondition, but fortunatelv it is not common in our Dractice.

G. P. BURNS

J. W. LAWS.Departments of Surgery and Radiodiagnosis,

Postgraduate Medical School,Ducane Road, London W.12.

EFFECTS OF PARTIAL GASTRECTOMY

G. R. THOMPSONG. NEALEJ. M. WATTSC. C. BOOTH.

Postgraduate Medical School,Ducane Road, London W.12.

SIR,-We thank Dr. Morgan and his colleagues for theircomments (April 2) and agree that our post-gastrectomypatients were a selected sample and that those studied in detailwere few in number. We continue to differ, however, aboutthe significance of a raised serum-alkaline phosphatase (S.A.P.)after partial gastrectomy. The association of a raised S.A.P.,without other obvious cause, with subnormal levels of vitamin-D-like activity in the plasma, skeletal rarefaction, and an

abnormal calcium infusion test, even in the presence of an

apparently normal bone-biopsy, suggests to us that the bio-chemical abnormality is due to vitamin-D deficiency, particu-larly when there is response to oral or intravenous, rather thanintramuscular, vitamin D. This is the situation that we referredto as

" subclinical osteomalacia ".Dr. Morgan and his colleagues may well be right in suggest-

ing that we have been missing significant microscopic changesin the past. But Dr. Ph. Bordier and Dr. H. Matrajt, of theCentre du Metabolisme Phosphocalcique, Paris, have examineda bone-biopsy from one of our patients with subclinical osteo-malacia ; they report that the undecalcified sections of bone,stained with ’ Solochrome Cyanine R’, were normal on allthe criteria mentioned by Dr. Morgan and his colleagues,although this patient had shown a biochemical response tovitamin D. Dr. Bordier and Dr. Matrajt did notice, however:that in certain other respects the biopsy was not entirely normal.These abnormalities are being investigated further and will bereported as soon as their significance has been assessed.

CONTAMINATED IRRIGATING FLUID

SIR,-Dr. Last and his colleagues (Jan. 8) describe bac-teraemia after urological instrumentation, and Dr. Mitchelland his colleagues (April 9) report urinary-tract infectionscaused by contaminated irrigating fluid.

In a study of postoperative urinary infection at this hospitalan organism was found in the urine of 30 gynoccologicalpatients during bladder drainage by indwelling catheter. Thebacterium, which was oxidase-positive, was most nearlyidentified as Alcaligenes fcecalis, and like the commonestisolate of Dr. Last and his colleagues it seemed to be a " waterorganism ". In most patients these organisms were foundintermittently and usually in small numbers, but in a fewinstances repeated cultures showed a heavy growth sometimeswith pyuria. The organisms, like those found by Dr. Last andhis colleagues, were presumably of low pathogenicity, butperhaps capable of infecting subjects particularly liable to

urinary-tract infection.Investigations showed that the spigots used for closure

of the catheters were heavily contaminated with this " waterorganism" as was the jar of 0-1% chlorhexidine solution inwhich the spigots were stored after disinfection by boiling.When artery forceps were used in place of spigots for theclosure of drainage tubing this organism was no longer foundin urine specimens.

Laboratory tests showed that the organism would multiplyfrom a small inoculum in 0- 1 % chlorhexidine in distilled water.It is, however, no new observation that there are bacteriacapable of surviving in chlorhexidine solutions; the manufact-

1. Matrajt, H., Hioco, D. Stain Technol. 1966, 41, 97.

urers themselves have drawn attention to this. Corks providea well-known source of bacteria; I have isolated Pseudomonaspyocyanea (Ps. aeruginosa), and organisms of either the mima orthe alkaligenes group from a high proportion of corks in stock-bottles of distilled water and chlorhexidine. Anderson et al.lhave shown that even when bacteria are susceptible to thedisinfectant transitory contamination may occur. The use of

screw-caps and glass or plastic stoppers avoids this hazard,but if chlorhexidine solutions are to be introduced into bodycavities-e.g., the bladder-they should be first heat-sterilised.These findings provide yet another illustration of the

difficulties of attempting to sterilise or to maintain the sterilityof surgical equipment by immersion in disinfectant solution.Disposable spigots for drainage tubes and catheters may nowbe obtained, packed singly, and sterilised by y-irradiation.

C. DULAKEELIZABETH KIDD.King’s College Hospital,

London S.E.5.

VIRUS VACCINE AND ANTILYMPHOCYTE SERUM

M. F. A. WOODRUFF.Department of Surgical Science,

Medical School,University of Edinburgh.

SIR,-Reports from this department that the survival ofskin homografts is greatly prolonged in rats treated withheterospecific antilymphocytic serum (A.L.S.) appear to havestimulated considerable interest in this material. More recent

experiments in which dogs bearing kidney homotransplantswere treated with horse-antidog-A.L.s. have proved equallyencouraging so far as transplant survival is concerned. Twoof eight treated dogs, however, died of distemper, althoughthey had been actively immunised by a commercial vaccinecontaining live attenuated distemper virus, and it seems justpossible that the infection was due to activation of virus

persisting in these animals. The experiments are being fullyreported.3 Since we and, we believe, others have preparedhorse-antihuman-A.L.s. for possible therapeutic use in renaltransplant recipients and patients with autoimmune disease,however, it seems desirable to draw attention to the risk of viralinfection which the use of this serum may entail.

In sounding this note of caution I am not suggesting that thedanger is insurmountable, or indeed that it should necessarilyprohibit cautious clinical trial at the present time. There are,for example, patients who continue to reject a renal transplantdespite all other forms of treatment, and for whom no placecan be found in a chronic dialysis programme, in whom theuse of A.L.S. might be justified. But pending further investiga-tion it would certainly seem unwise to administer A.L.S. to anypatient who has been inoculated with living poliomyelitisvaccine.

RESPONSE TO PHYTOHÆMAGGLUTININ

SIR,-Some confusion may arise from Dr. Elves’ remarks inhis letter (April 16) on the role of serum-factors in cultures ofstimulated lymphocytes. His findings suggest that plasma-factors are of little importance in chronic lymphocytic leukaemia,and that the main variable is the lymphocyte itself. In makingthis point Dr. Elves gives the impression that the source ofhuman serum used for culture is immaterial. That there areimportant serum and plasma factors in normal and pathologicalhuman blood-samples can be shown,4 as well as in blood fromother species. The work of Dr. Elves and his colleagues(March 26) would itself give some support to this suggestion.Using the mixed lymphocyte reaction in plasma from urxmicpatients before and after dialysis they found improved trans-

1. Anderson, K., Keynes, R. Br. med. J. 1958, ii, 274.2. Woodruff, M. F. A., Anderson, N. F. Nature, Lond. 1963, 200, 702;

Ann. N.Y. Acad. Sci. 1964, 120, 119.3. Abaza, H. M., Nolan, B., Watt, J. G., Woodruff, M. F. A. Unpublished;

Woodruff, M. F. A., Anderson, N. F., Abaza, H. M. in LymphocyteSymposium (edited by J. M. Yoffey). London (in the press).

4. Holt, P. J. L., Ling, N. R., Stanworth, D. R. Immunochemistry (in thepress).

5. Holt, P. J. L., Ling, N. R. Unpublished.6. Metcalf, W. K. Expl. Cell. Res. 1965, 40, 490.