402
ferin-luciferase reagent was not sufficently sensitive to detect 10’ bacteria/ml. In our hands the method has proved more reliable in this respect than the generally
accepted cultural method. Specificity in the method depends on the removal of non-bacterial A.T.P. derived principally from cellular elements. High cell-counts in the absence of bacteria did not give rise to false-positive results. In this respect our method is superior to the automated chemiluminescent test which uses alkaline luminol.6 Positive results were found in patients where the growth of bacteria was suppressed due to intercurrent therapy with antibacterial drugs. This emphasises that bioluminescence measurements are related to total bacterial content rather than to numbers of viable organisms, which may account for the relatively low specificity when compared with the pour-plate technique. In those urine samples found to be positive, relatively elaborate cultural techniques should be used to detect, for example, cell-wall-deficient or anaerobic
Preliminary Communication DIALYSIS PROCEDURES IN ACUTE LIVER COMA ALAN
DAVID C. DUKES J. KNELL Warwick Hospital, and Walsgrave Hospital, Coventry
Summary
9 to
hæmodialyses against fluids designed reduce plasma abnormality were used
in four patients with acute liver failure in an attempt to maintain consciousness and buy time for liver regeneration. Dialysis had little effect in two patients. In the third patient spontaneous movements and response to commands were seen during the second dialysis. Arousal occurred during both dialyses in the fourth patient who
eventually recovered. which may complicate acute liver failure is consequence of abnormal plasma composition.Loss of liver regulation cripples the systems controlling the internal environment, which are then loaded by degradation products released from the necrotic liver. The pattern of known plasma abnormalities is a characteristic of acute liver failure, and the clinical picture is distinctive and consistent. 1-3 Treatment of coma in acute liver failure must involve restoration of normal plasma composition. A means of artificially controlling the internal environment is required: biological procedures are unreliable and expensive.4 Haemodialysis can be used to artificially control the internal environment by means of dialysate fluids designed to reduce the plasma abnormalities. A clinical trial of this procedure is in progress in Warwick Hospital. In the first year we have conducted nine dialyses in four patients, and we can now make a provisional assessment of the technique. coma
a
PATIENTS AND METHODS
The
It has been stated’ that automation in microbiology will aid rapid diagnosis in several ways Urine specimens form the largest part of the workload of the microbiology laboratory. This test identifies negative specimens quickly, and will allow the resources of the laboratory to be concentrated where they will be of most value. this
treatment.
Requests for reprints should be addressed to H.H.J., BactenologB Department, Gibson Laboratories, Radcliffe Infirmary, Oxford OX2 6HE, from whom further details of the continuous-flow system may be obtained. REFERENCES
Kass, E. H. Trans. Ass. Am. Physns, 1956, 69, 56. MacKinnon, A. E., Strachan, C. J. L., Sleigh, J. D., Burns, M. M. in Uri nary Tract Infection (edited by W. Brumfitt and A. W. Asscher). London. 1973. 3. Chappelle, E. W., Levin, G. V. Biochem. Med. 1968, ii, 41. 4. McGeachie, J., Kennedy, A. C. J. clin. Path. 1963, 16, 32. 5. Conn, R. B., Charache, P., Chappelle, E. W. Am. J. clin. Path. 1975, 63, 1. 2.
493. 6. Ewetz, L., Strangert, K. Acta 7. Lancet, 1973, ii, 1306.
path.
microbiol. scand.
(B), 1974, 82, 375.
tients treated. Routine support included intravenous glucose, a daily enema, oral potassium sulphate 0-3 g g twice daily as a stool-acidifying laxative,5 and bowel sterilisation with oral streptomycin 0.5 g twice daily. Dexamethasone was given when there was cerebral oedema. Seizures were controlled with of diazenitrous-oxide/oxygen (’Entonox’) or 1-2 pam. Arteriovenous shunts were constructed under local anxsthetic. ’Cuprophane’ coils (EX03, Extracorporeal Company, New York) were used for dialysis. The first two patients were dialysed against 100 1 fluid batches in a Kolff recirculating artificial kidney. The dialysate contained electrolytes, glucose, and eighteen aminoacids at normal plasma concentrations. Phosphate (1mmol/l) buffered the hydrogen ion concentration to 40 nmol/1. Each bath was continued for two hours. Fresh frozen plasma, one unit twelve hourly, was given. The procedure was then modified to increase dialysis efficiency. A Lucas Mk.I single-pass monitor consumed 350-500 ml/min of dialysate with the following composition: sodium 140, potassium 4.5, calcium 2.5, magnesium 1.2, chloride 98, bicarbonate 25, and acetate 28-5 mmol/l; glucose 10 mmoJ;1: glycine 250, alanine 300, valine 300, leucine 175, isoleucine 100, proline 110, serine 120, threonine 120, cysteine 90, lysine ’, 125, ornithine 50, arginine 75, and histidine 50 µmol/l. The phosphate buffer was omitted. Dialyses lasted four hours, and two units of fresh frozen plasma were infused into the coil arterial line at the start of each. In all patients coil blood-8(M was 150-300 ml/min. Heparin was infused at 2500 units/h
mg doses
.
INTRODUCTION
THE
organisms, but only about 30% of specimens will require
accompanying table gives clinical details of the four pa-
’
during dialysis. The dialyses were well tolerated. In the first two patients transient tachycardia and hypotension developed soon after starting dialysis. Later this was avoided by keeping the coil blood-flow below 100 ml/min until the plasma had been given CLINICAL DETAILS OF PATIENTS TREATED
403 The limited permeability of cuprophane restricts the effectiveness of dialysis. The dialysates used so far contain substances of molecular weight up to 180, yet cuprophane membranes have not allowed equilibration in a sufficiently short length of time. A substantial increase in membrane area is not practicable, and more permeable membrane materials are needed. We do not know how much control of the internal environment is necessary to maintain consciousness. The present procedure is intended to restore the normal plasma concentrations of electrolytes, glucose, and aminoacids. The dialysate composition may need to be modified as knowledge increases. Substances at present controlled may not be critical, and new factors may prove important. Tryptophan is an example of a substance which may be important but which is not regulated by the present procedure. Acetate may not be a safe counter-anion in dialysates used in liver failure. We hope to achieve a means of short-term metabolic support during acute liver failure, to buy time for regeneration. Long-term artificial liver replacement by this procedure will probably not be possible. If effective support keeps a patient alive but there is no liver regener-
! Plasma phenylalanine and
hses. Shaded
area
tyrosine concentrations before
represents desirable
Blood contained in the the end of dialysis.
plasma
and after 5 dia-
concentration.
dialyser was returned to
the
patient
at
ation, then transplantation would offer the only hope for survival. We believe that treatment should be given early for best results. Our indication at present is the onset of coma. This may be changed to the onset of encephalopathy. The ideal indication would be biochemical, but no reliable index is available at present. ,
medical, nursing, and laboratory colleagues at Warwick Richardson; Mr R. Adamson; Mr F. Roberts and the renal unit technicians; and Mrs Heather Dukes. Reprint requests to A.J.K. at Warwick Hospital. We thank
our
Hospital;
Mr R. W.
REFERENCES
RESULTS
In patients 1 and 2 dialysis had little effect. The singlepartial arousal during the second dialysis in patient 3, indicated by spontaneous movements and response to commands. Arousal occurred during each dialysis in patient 4, with relapse between diaivses. In patient 4 minor relapse after the second dialysis was followed by recovery. Blood-clotting was improved remarkably. The prothrombin-time was restored and the correction was sustained. Plasma was given during dialysis, but the degree )f improvement was unexpected. Perhaps there is a dialysable circulating anticoagulant in liver failure, or ’11aybe the effect of infused plasma is increased by remo,alof citrate. Correction of the aminoacid pattern was incomplete. After dialysis plasma phenylalanine and tyrosine concentrations were reduced (see accompanying figure); iasma-methionine fell; valine, leucine, and isoleucine .mcentrations increased. There was no detectable bacterial growth in the dialyates, which were freshly made up without antibiotics. pass procedure led to
DISCUSSION
Weare encouraged
by these initial results. Evaluation
. the procedure will require further trials, preferably in everal centres. It seems to be safe, provided only that fluid lost by ultrafiltration is replaced. We had no probems with bleeding or blood-cell destruction. No patient
riorated as a result of dialysis in this small series.
Knell, A. J., Pratt, O. E., Curzon, G., Williams, R. Eighth Symposium on Advanced Medicine (edited by G. Neale); p. 156. London, 1972. 2. Papers in Artificial Liver Support (edited by R. Williams and I. M. MurrayLyon); London, 1975. 3. Munro, H. N., Fernstrom, J. D., Wurtman, R. J. Lancet, 1975, i, 722. 4. Sherlock, S. Diseases of the Liver and Biliary System; p. 118. Oxford, 1975. 5. Agostini, L., Down, P. F., Murison, J., Wrong, O. M. Gut, 1972, 13, 859. 1.
Reviews of Books Dermatological Photobiology Clinical and Experimental Aspects. I. A. MAGNUS, F.R.C.P., Instiof Dermatology, London. Oxford: Blackwell. 1976. Pp. 292.
tute
£9.75. LONG awaited, this distillation of many years’ research and practical experience in a notably difficult area is welcomed. The subject is difficult not because any one part of it is impossibly arcane but because so many different disciplines must be mastered to achieve a full understanding. A working knowledge of photophysics, photochemistry, meteorology, lighting technology, applied optics, and environmental physiology is necessary before the final target-the skin-can itself be properly studied. Throughout the world there can be few individuals qualified to write authoritatively on this subject, and of these Professor Magnus is perhaps the most distinguished. British dermatology, and St. John’s Hospital, are fortunate to have witnessed his pioneering efforts from the beginning. His book indicates wide scholarship, both classical and scientific, but can also be used as a practical handbook by those who need a working knowledge of this specialised but important part of dermatology. Even in this umbrageous island dermatologists daily encounter in their clinics the effects of actinic damage
ferin-luciferase reagent was not sufficently sensitive to detect 10’ bacteria/ml. In our hands the method has proved more reliable in this respect than the generally
accepted cultural method. Specificity in the method depends on the removal of non-bacterial A.T.P. derived principally from cellular elements. High cell-counts in the absence of bacteria did not give rise to false-positive results. In this respect our method is superior to the automated chemiluminescent test which uses alkaline luminol.6 Positive results were found in patients where the growth of bacteria was suppressed due to intercurrent therapy with antibacterial drugs. This emphasises that bioluminescence measurements are related to total bacterial content rather than to numbers of viable organisms, which may account for the relatively low specificity when compared with the pour-plate technique. In those urine samples found to be positive, relatively elaborate cultural techniques should be used to detect, for example, cell-wall-deficient or anaerobic
Preliminary Communication DIALYSIS PROCEDURES IN ACUTE LIVER COMA ALAN
DAVID C. DUKES J. KNELL Warwick Hospital, and Walsgrave Hospital, Coventry
Summary
9 to
hæmodialyses against fluids designed reduce plasma abnormality were used
in four patients with acute liver failure in an attempt to maintain consciousness and buy time for liver regeneration. Dialysis had little effect in two patients. In the third patient spontaneous movements and response to commands were seen during the second dialysis. Arousal occurred during both dialyses in the fourth patient who
eventually recovered. which may complicate acute liver failure is consequence of abnormal plasma composition.Loss of liver regulation cripples the systems controlling the internal environment, which are then loaded by degradation products released from the necrotic liver. The pattern of known plasma abnormalities is a characteristic of acute liver failure, and the clinical picture is distinctive and consistent. 1-3 Treatment of coma in acute liver failure must involve restoration of normal plasma composition. A means of artificially controlling the internal environment is required: biological procedures are unreliable and expensive.4 Haemodialysis can be used to artificially control the internal environment by means of dialysate fluids designed to reduce the plasma abnormalities. A clinical trial of this procedure is in progress in Warwick Hospital. In the first year we have conducted nine dialyses in four patients, and we can now make a provisional assessment of the technique. coma
a
PATIENTS AND METHODS
The
It has been stated’ that automation in microbiology will aid rapid diagnosis in several ways Urine specimens form the largest part of the workload of the microbiology laboratory. This test identifies negative specimens quickly, and will allow the resources of the laboratory to be concentrated where they will be of most value. this
treatment.
Requests for reprints should be addressed to H.H.J., BactenologB Department, Gibson Laboratories, Radcliffe Infirmary, Oxford OX2 6HE, from whom further details of the continuous-flow system may be obtained. REFERENCES
Kass, E. H. Trans. Ass. Am. Physns, 1956, 69, 56. MacKinnon, A. E., Strachan, C. J. L., Sleigh, J. D., Burns, M. M. in Uri nary Tract Infection (edited by W. Brumfitt and A. W. Asscher). London. 1973. 3. Chappelle, E. W., Levin, G. V. Biochem. Med. 1968, ii, 41. 4. McGeachie, J., Kennedy, A. C. J. clin. Path. 1963, 16, 32. 5. Conn, R. B., Charache, P., Chappelle, E. W. Am. J. clin. Path. 1975, 63, 1. 2.
493. 6. Ewetz, L., Strangert, K. Acta 7. Lancet, 1973, ii, 1306.
path.
microbiol. scand.
(B), 1974, 82, 375.
tients treated. Routine support included intravenous glucose, a daily enema, oral potassium sulphate 0-3 g g twice daily as a stool-acidifying laxative,5 and bowel sterilisation with oral streptomycin 0.5 g twice daily. Dexamethasone was given when there was cerebral oedema. Seizures were controlled with of diazenitrous-oxide/oxygen (’Entonox’) or 1-2 pam. Arteriovenous shunts were constructed under local anxsthetic. ’Cuprophane’ coils (EX03, Extracorporeal Company, New York) were used for dialysis. The first two patients were dialysed against 100 1 fluid batches in a Kolff recirculating artificial kidney. The dialysate contained electrolytes, glucose, and eighteen aminoacids at normal plasma concentrations. Phosphate (1mmol/l) buffered the hydrogen ion concentration to 40 nmol/1. Each bath was continued for two hours. Fresh frozen plasma, one unit twelve hourly, was given. The procedure was then modified to increase dialysis efficiency. A Lucas Mk.I single-pass monitor consumed 350-500 ml/min of dialysate with the following composition: sodium 140, potassium 4.5, calcium 2.5, magnesium 1.2, chloride 98, bicarbonate 25, and acetate 28-5 mmol/l; glucose 10 mmoJ;1: glycine 250, alanine 300, valine 300, leucine 175, isoleucine 100, proline 110, serine 120, threonine 120, cysteine 90, lysine ’, 125, ornithine 50, arginine 75, and histidine 50 µmol/l. The phosphate buffer was omitted. Dialyses lasted four hours, and two units of fresh frozen plasma were infused into the coil arterial line at the start of each. In all patients coil blood-8(M was 150-300 ml/min. Heparin was infused at 2500 units/h
mg doses
.
INTRODUCTION
THE
organisms, but only about 30% of specimens will require
accompanying table gives clinical details of the four pa-
’
during dialysis. The dialyses were well tolerated. In the first two patients transient tachycardia and hypotension developed soon after starting dialysis. Later this was avoided by keeping the coil blood-flow below 100 ml/min until the plasma had been given CLINICAL DETAILS OF PATIENTS TREATED
403 The limited permeability of cuprophane restricts the effectiveness of dialysis. The dialysates used so far contain substances of molecular weight up to 180, yet cuprophane membranes have not allowed equilibration in a sufficiently short length of time. A substantial increase in membrane area is not practicable, and more permeable membrane materials are needed. We do not know how much control of the internal environment is necessary to maintain consciousness. The present procedure is intended to restore the normal plasma concentrations of electrolytes, glucose, and aminoacids. The dialysate composition may need to be modified as knowledge increases. Substances at present controlled may not be critical, and new factors may prove important. Tryptophan is an example of a substance which may be important but which is not regulated by the present procedure. Acetate may not be a safe counter-anion in dialysates used in liver failure. We hope to achieve a means of short-term metabolic support during acute liver failure, to buy time for regeneration. Long-term artificial liver replacement by this procedure will probably not be possible. If effective support keeps a patient alive but there is no liver regener-
! Plasma phenylalanine and
hses. Shaded
area
tyrosine concentrations before
represents desirable
Blood contained in the the end of dialysis.
plasma
and after 5 dia-
concentration.
dialyser was returned to
the
patient
at
ation, then transplantation would offer the only hope for survival. We believe that treatment should be given early for best results. Our indication at present is the onset of coma. This may be changed to the onset of encephalopathy. The ideal indication would be biochemical, but no reliable index is available at present. ,
medical, nursing, and laboratory colleagues at Warwick Richardson; Mr R. Adamson; Mr F. Roberts and the renal unit technicians; and Mrs Heather Dukes. Reprint requests to A.J.K. at Warwick Hospital. We thank
our
Hospital;
Mr R. W.
REFERENCES
RESULTS
In patients 1 and 2 dialysis had little effect. The singlepartial arousal during the second dialysis in patient 3, indicated by spontaneous movements and response to commands. Arousal occurred during each dialysis in patient 4, with relapse between diaivses. In patient 4 minor relapse after the second dialysis was followed by recovery. Blood-clotting was improved remarkably. The prothrombin-time was restored and the correction was sustained. Plasma was given during dialysis, but the degree )f improvement was unexpected. Perhaps there is a dialysable circulating anticoagulant in liver failure, or ’11aybe the effect of infused plasma is increased by remo,alof citrate. Correction of the aminoacid pattern was incomplete. After dialysis plasma phenylalanine and tyrosine concentrations were reduced (see accompanying figure); iasma-methionine fell; valine, leucine, and isoleucine .mcentrations increased. There was no detectable bacterial growth in the dialyates, which were freshly made up without antibiotics. pass procedure led to
DISCUSSION
Weare encouraged
by these initial results. Evaluation
. the procedure will require further trials, preferably in everal centres. It seems to be safe, provided only that fluid lost by ultrafiltration is replaced. We had no probems with bleeding or blood-cell destruction. No patient
riorated as a result of dialysis in this small series.
Knell, A. J., Pratt, O. E., Curzon, G., Williams, R. Eighth Symposium on Advanced Medicine (edited by G. Neale); p. 156. London, 1972. 2. Papers in Artificial Liver Support (edited by R. Williams and I. M. MurrayLyon); London, 1975. 3. Munro, H. N., Fernstrom, J. D., Wurtman, R. J. Lancet, 1975, i, 722. 4. Sherlock, S. Diseases of the Liver and Biliary System; p. 118. Oxford, 1975. 5. Agostini, L., Down, P. F., Murison, J., Wrong, O. M. Gut, 1972, 13, 859. 1.
Reviews of Books Dermatological Photobiology Clinical and Experimental Aspects. I. A. MAGNUS, F.R.C.P., Instiof Dermatology, London. Oxford: Blackwell. 1976. Pp. 292.
tute
£9.75. LONG awaited, this distillation of many years’ research and practical experience in a notably difficult area is welcomed. The subject is difficult not because any one part of it is impossibly arcane but because so many different disciplines must be mastered to achieve a full understanding. A working knowledge of photophysics, photochemistry, meteorology, lighting technology, applied optics, and environmental physiology is necessary before the final target-the skin-can itself be properly studied. Throughout the world there can be few individuals qualified to write authoritatively on this subject, and of these Professor Magnus is perhaps the most distinguished. British dermatology, and St. John’s Hospital, are fortunate to have witnessed his pioneering efforts from the beginning. His book indicates wide scholarship, both classical and scientific, but can also be used as a practical handbook by those who need a working knowledge of this specialised but important part of dermatology. Even in this umbrageous island dermatologists daily encounter in their clinics the effects of actinic damage
