- Email: [email protected]
LCAT activity as a prognostic liver function test
249
Although non-Hodgkin lymphoma is associated with HIV infection and AIDS,z this tumour has been regarded as an infrequent complication of HIV infection. Our preliminary data indicate that the risk of non-Hodgkin lymphoma is directly associated with degree of immunosuppression in people with HIV infection, as it is in transplant recipients.3 This contrasts with the risk of Kaposi’s sarcoma, which can occur with less severe immunodeficiency.4 Beral et al report that the proportion of AIDS cases defined by Kaposi’s sarcoma has declined in the US, but in our cohort the incidence of Kaposi’s sarcoma has increased. These findings are consistent with pathogerietically different cofactors for HIV-associated Kaposi’s sarcoma and non-Hodgkin lymphoma, as well as the spectre of substantial increases in AIDS-associated malignant disease as survival improve5 Viral Epidemiology Section, National Cancer Institute, Rockville, MD 20852, USA
CHARLES S. RABKIN
JAMES J. GOEDERT
et al. Effect of T4 count and cofactors on the homosexual men infected with human immunodeficiency virus. JAMA 1987; 257: 331-34. 2. Biggar RJ, Horm J, Lubin JH, Goedert JJ, Greene MH, Fraumeni JF Cancer trends in a population at nsk of acquired immunodeficiency syndrome. J Natl Cancer Inst
1. Goedert
JJ, Biggar RJ, Melbye M,
incidence of AIDS
m
1985; 74: 793-97. Why do immunosuppressed patients develop cancer? Crit Rev Oncogenesis 1989; 1: 27-52. 4. Rabkin CS, Goedert JJ, Biggar RJ, Blattner WA. Kaposi’s sarcoma in three HIV-infected cohorts. J Acq Immun Def Synd (in press). 5 Pluda JM, Yarchoan R, Jaffe ES, et al. Development of opportunistic non-Hodgkin’s lymphoma in a cohort of patients with severe HIV infection on long-term antiretroviral therapy. Ann Intern Med (in press) 3 Penn I.
Indirect memory for words presented anaesthesia
during
SIR,-Recent evidence suggests that information-processing during unconsciousness induced by general anaesthesia.1,22 Some controversy remains over the validity of this evidenced A new approach is to test memory indirectly,’ clearly demonstrating in a large sample processing of neutral verbal stimuli (ie, stimuli without emotional connotation) during adequate general anaesthesia. The present study was initiated to validate these results, using the same experimental pattern but with a different anaesthetic technique. Forty-one female and nine male (mean age 38 years, range 19-71) surgical patients, scheduled for elective procedures under general anaesthesia, were studied. None of the patients had hearing difficulties or a history of alcohol or psychoactive-drug abuse. The patients were allocated randomly, evenly, and double blind to experimental or control groups. Preoperative anxiety was assessed in the afternoon before surgery by each patient completing the state version of the State-Trait anxiety inventory. From the time of skin incision, all patients were played an audiotape via headphones. The headphones prevented patients hearing sounds from the operating theatre and the experimenter hearing the tape. occurs
The control tape contained 20 min of seaside sounds. The experimental tape comprised 5 min of seaside sounds followed by 30 presentations over 15 min of the four "target" words "yellow", "banana", "green", and "pear". The words had been recorded, in the above order, at a speed of one word every 15s, preceded by the warning phrase: "Please listen carefully", with an interval between series of about 20 s. The tapes for both groups were identical and had been coded A and B by someone not involved in the experiment. Any experimenter bias caused by non-conscious observation of patterns in the data was prevented by recoding the tapes halfway through the study. Only after all data had been collected were the codes broken. After 20 min, a different tape with seaside sounds was played to all patients for the remainder of the
operation. Anaesthesia was induced with thiopentone and droperidol, and atracurium or pancuronium was used for muscle relaxation. Maintenance took place with 66% nitrous oxide in oxygen, supplemented with sufentanil or fentanyl. Each patient was interviewed as soon as possible after surgery (mean interval between start of second tape and postoperative testing 81 min, range 30-179). Patients were asked about any recall
of intraoperative events. They were then invited to name the first three examples of of a non-experimental category "vegetables" and the experimental categories "fruit" and "colours" that came to mind. Any cited word corresponding to one of those presented during anaesthesia was scored at a "hit". A maximum of four hits could thus be obtained. A one-tailed Student’s t-test was carried out to determine whether the groups differed in the number of hits. There were no significant differences between the groups with respect to age, duration of surgery, preoperative anxiety and number of previous operations. No patient recalled intraoperative events. The mean (SEM) number of hits for the experimental group was 2-4 (0-18) and for the control group 1 ’84 (0-2) (t = 2-8, df=48, p < 0025). There was no significant difference between groups with respect to the non-experimental category "vegetables". The results suggest that even neutral auditory stimuli are registered in the anaesthetised cortex. Our findings accord with Roorda-Hrdlickova and colleagues,4 who used a different anaesthetic technique. In that study anaesthesia was induced with propofol and maintained with nitrous oxide in oxygen and isoflurane. It is, therefore, unlikely that auditory informationprocessing is restricted to rare occasions or particular anaesthetic cocktails. We seem to be "just scratching the surface of this important issue", as Millers put it. Unconscious perception of auditory stimuli during general anaesthesia has substantial implications. Inappropriate or ambiguous remarks "overheard" during surgery may lead to psychological disturbances or delayed postoperative recovery6. It has therefore been suggested that anaesthetised patients should be provided with earplugs.7,8 We recommend instead the use of therapeutic suggestions during anaesthesia, which may have a beneficial effect on the postoperative course.9 We thank the
patients who participated in this study, the departments of anaesthesia, general surgery, and plastic and reconstructive surgery at the St Lucas Hospital, Amsterdam, Dr J. N. Keeman, Prof J. G. Bovill, Prof J. G. Jones, and Prof K. Millar. Department of Medical Psychology and Psychotherapy, Erasmus University, 3000 DR Rotterdam, Netherlands
M. JELICIC B. BONKE
Department of Anaesthesia, Hospital, Amsterdam
D. K. APPELBOOM
St Lucas
1. Editorial. Advertising dunng anaesthesia? Lancet 1986; ii: 1019-20. 2. Bonke B, Fitch W, Millar K, eds. Memory and awareness in anaesthesia. Amsterdam: Swets & Zeitlinger, 1990. 3. Wilson ME, Spiegelhalter D. Awareness during anaesthesia. Lancet 1986; ii: 1338 4. Roorda-Hrdličková V, Wolters G, Bonke B, Phaf RH Unconscious perception during general anaesthesia, demonstrated by an implicit memory task. In: Bonke B, Fitch W, Millar K, eds. Memory and awareness in anaesthesia. Amsterdam: Swets & Zeitlinger, 1990: 150-55. 5. Miller RD, ed The year book of anesthesia. Chicago. Year Book Medical Publishers
Inc, 1989: 7-9
awakening paralyzed during surgery. A syndrome of traumatic JAMA 1975; 234: 67-68. 7. Scott DL. Awareness during general anaesthesia. Can Anaesth Soc J 1972; 19: 173-83. 8. Davis R. Anaesthesia, amnesia, dreams and awareness. Med J Aust 1987; 146: 4-5. 9. Evans C, Richardson PH. Improved recovery and reduced postoperative stay after therapeutic suggestions during general anaesthesia. Lancet 1988; ii 491-93. 6. Blacher RS. On neurosis.
LCAT activity
as a
prognostic liver function test
SIR,-Assessment of liver function depends on crude measures of synthetic capability (albumin, prothrombin time), hepatocyte damage (aminotransferases), and cholestasis (bilirubin). Although such measures provide information about the immediate functional state of the liver, they are rarely useful in the prediction of outcome of liver disease, and only serum bilirubin is accepted as having a prognostic role for patients with primary biliary cirrhosis.1 However, accurate prediction of prognosis is important in decisions about orthotopic liver transplantation. Are there other, more specific measures of liver function that may prove useful in the determination of outcome? Lecithin cholesterol acyltransferase (LCAT, EC 2.3.1.43) catalyses the esterification of cholesterol in plasma, is synthesised predominantly by the liver, and is a sensitive measure of liver
250
Endoscopic correction of primary vesicoureteric reflux SIR,-Mr Puri (June 2, p 1320) describes a simple and effective technique (about whose long-term effects we have greater reservations than he) for the abolition of the radiological appearance of vesicoureteric reflux (VUR), but he does not discuss its benefit to
patients. In particular, we would like to have evidence of a causal association between VUR and morbidity and to know how effectively such intervention may reduce the reflux. We also question the wisdom of the adoption of a data-collection protocol in which the subjects (mainly girls) would have annual micturating cystouretheography for up to five years. Paediatric Department, Southmead Hospital, Bristol BS10 5NB, UK
*** This letter has been shown - ED. L.
Modified Child - Pugh Class
Plasma LCAT activity measured by proteoliposome method in healthy controls and cirrhotic patients. Horizontal bars=mean, vertical bars=SEM.
function.2,3 We used the proteoliposome method4 to measure plasma LCAT activity in 28 patients with histologically confirmed cirrhotic liver disease (16 with alcoholic cirrhosis; 7 primary biliary cirrhosis; 5 cryptogenic cirrhosis) and 20 healthy volunteers. This method uses a well-defined exogenous substrate; it does not have the inaccuracies of other techniques;2,3 and the values obtained are closely related to LCAT concentration.5 We found a clear difference between the LCAT activities of healthy subjects and patients (mean 119.0 [SEM 84] 39-8 [53] nmol/ml per hour; p < 0-001) with normal values in only 2 patients. Moreover, LCAT activity significantly correlated with modified Child-Pugh scores (by linear regression r = - 0-483; p=0011; figure) indicating that it may be a powerful additional test for the precise definition of severity and outcome of liver disease. Plasma LCAT activity has been reported as a predictor of early allograft function in transplant recipients6 and of viability of allograft donors. We now propose incorporation of LCAT measurement into models assessing the best timing for liver transplantation, especially since previous models have so far failed to offer any useful clinical application.8 Hepato-biliary and Liver Transplantation Unit, Royal Free Hospital,
RICHARD C. HORTON
London NW3 2QG, UK
JAMES S. OWEN
Rydning A, Schrumdf E, Abdelnoor M, Elgjo K, Jenssen E. Factors of prognostic importance in primary biliary cirrhosis. Scand J Gastroenterol 1990; 25: 119-26. 2. Martiis MD, Barlattani A, Parenzi A, Sebastiani F. Pattern of LCAT activity m the course of liver cirrhosis. J Int Med Res 1983; 11: 232-38. 3. Simko V, Kelley RE, Dincsoy HP. Predicting severity of liver disease: twelve laboratory tests evaluated by multiple regression. J Int Med Res 1985; 13: 249-54. 4. Chen C, Albers JJ. Characterisation of proteoliposomes containing apoprotein A1: a new substrate for the measurement of lecithin: cholesterol acyltransferase activity. J Lipid Res 1982; 23: 680-91. 5. Floren CH, Chen C-H, Franzen J, Albers JJ. Lecithin: cholesterol acyltransferase m liver disease. Scand J Clin Lab Invest 1987; 47: 613-17. 6. Shimada M, Yanaga K, Makowka L, Kakizoe S, van Thiel DH, Starzl TE. Significance of LCAT activity as a prognostic indicator of early allograft function in clinical liver transplantation. Transplantation 1989; 48: 600-03. 7. Higashi H, Yanaga K, Shimada M, Makowka L, van Thiel DH, Starzl TE. Plasma LCAT activity in multiple organ donors: a predictor of allograft viability in clinical liver transplantation. Transplantation Proc 1990; 22: 433-34. 8. Keiding S, Ericzon BG, Eriksson S, et al. Survival after liver transplantation of patients with primary biliary cirrhosis in the Nordic countries Scand J 1.
Gastroenterol 1990; 25: 11-18.
T. L. CHAMBERS
J. D. FRANK
to
Mr Puri, whose
reply follows.
SiR,—The management of vesicoureteric reflux in children has been very controversial. During the past three decades there have been over 5000 reports on this subject. The Birmingham Reflux Study is probably the best known of the studies that prospectively compared medical and surgical management of vesicoureteric reflux. This study showed that more than half the patients continued to show severe reflux after five years of medical treatment. What is to be done for these patients? Should they have a simple effective day-care procedure to stop reflux or should they embark on a lifetime of chemoprophylaxis? My investigation was not designed to address all aspects of vesicoureteric reflux-it was merely intended as a contribution to the controversy. With respect to the "annual" micturating cystourethrography, we initially closely monitored the results of this new procedure, but with further experience now do micturating cystourethrography at three months, at one year, and again at three years after endoscopic correction of reflux. The Birmingham Reflux Study Group who treat patients by chemoprophylaxis do micturating cystography at two years and five years. If reflux persists then presumably they go on
investigating.
Children’s Research Centre, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland 1.
PREM PURI
Birmingham Reflux Study Group. Prospective trial of operative versus nonoperative treatment of severe vesicoureteric reflux in children: five years observation. Br Med J 1987; 295: 237-41.
Non-coronary thrombolysis SIR,-We read with interest your editorial concerning noncoronary thrombolysis (March 24, p 691). This technique for the treatment of acute vascular ischaemia is one in which our unit has considerable experience. Whilst endorsing most of what was said, we would like to make some additional points. Not enough emphasis was placed on the use of recombinant tissue plasminogen activator (alteplase, r-TPA). Although individual series with r-TPA have not yet accrued sufficient numbers to reach statistical significance, without exception they show results superior to streptokinase treatment." Lysis times are shorter, limb loss and mortality rates lower, and thrombus specificity leads to less interference with the systemic haemostatic system and so to fewer haemorrhagic complications. We now use r-TPA as the agent of choice. Rethrombosis was cited in the editorial as a substantial problem. Our results have been encouraging in that three cases of rethrombosis after initial lysis have been re-cleared with r-TPA. Streptokinase cannot be used again in this context because of
possible allergic complications. We agree that if lysis is not well established by 12 h then thrombolysis is unlikely to succeed at that dose. However, the doses of r-TPA used in the UK (05 mg/h)’ are considerably less than
Although non-Hodgkin lymphoma is associated with HIV infection and AIDS,z this tumour has been regarded as an infrequent complication of HIV infection. Our preliminary data indicate that the risk of non-Hodgkin lymphoma is directly associated with degree of immunosuppression in people with HIV infection, as it is in transplant recipients.3 This contrasts with the risk of Kaposi’s sarcoma, which can occur with less severe immunodeficiency.4 Beral et al report that the proportion of AIDS cases defined by Kaposi’s sarcoma has declined in the US, but in our cohort the incidence of Kaposi’s sarcoma has increased. These findings are consistent with pathogerietically different cofactors for HIV-associated Kaposi’s sarcoma and non-Hodgkin lymphoma, as well as the spectre of substantial increases in AIDS-associated malignant disease as survival improve5 Viral Epidemiology Section, National Cancer Institute, Rockville, MD 20852, USA
CHARLES S. RABKIN
JAMES J. GOEDERT
et al. Effect of T4 count and cofactors on the homosexual men infected with human immunodeficiency virus. JAMA 1987; 257: 331-34. 2. Biggar RJ, Horm J, Lubin JH, Goedert JJ, Greene MH, Fraumeni JF Cancer trends in a population at nsk of acquired immunodeficiency syndrome. J Natl Cancer Inst
1. Goedert
JJ, Biggar RJ, Melbye M,
incidence of AIDS
m
1985; 74: 793-97. Why do immunosuppressed patients develop cancer? Crit Rev Oncogenesis 1989; 1: 27-52. 4. Rabkin CS, Goedert JJ, Biggar RJ, Blattner WA. Kaposi’s sarcoma in three HIV-infected cohorts. J Acq Immun Def Synd (in press). 5 Pluda JM, Yarchoan R, Jaffe ES, et al. Development of opportunistic non-Hodgkin’s lymphoma in a cohort of patients with severe HIV infection on long-term antiretroviral therapy. Ann Intern Med (in press) 3 Penn I.
Indirect memory for words presented anaesthesia
during
SIR,-Recent evidence suggests that information-processing during unconsciousness induced by general anaesthesia.1,22 Some controversy remains over the validity of this evidenced A new approach is to test memory indirectly,’ clearly demonstrating in a large sample processing of neutral verbal stimuli (ie, stimuli without emotional connotation) during adequate general anaesthesia. The present study was initiated to validate these results, using the same experimental pattern but with a different anaesthetic technique. Forty-one female and nine male (mean age 38 years, range 19-71) surgical patients, scheduled for elective procedures under general anaesthesia, were studied. None of the patients had hearing difficulties or a history of alcohol or psychoactive-drug abuse. The patients were allocated randomly, evenly, and double blind to experimental or control groups. Preoperative anxiety was assessed in the afternoon before surgery by each patient completing the state version of the State-Trait anxiety inventory. From the time of skin incision, all patients were played an audiotape via headphones. The headphones prevented patients hearing sounds from the operating theatre and the experimenter hearing the tape. occurs
The control tape contained 20 min of seaside sounds. The experimental tape comprised 5 min of seaside sounds followed by 30 presentations over 15 min of the four "target" words "yellow", "banana", "green", and "pear". The words had been recorded, in the above order, at a speed of one word every 15s, preceded by the warning phrase: "Please listen carefully", with an interval between series of about 20 s. The tapes for both groups were identical and had been coded A and B by someone not involved in the experiment. Any experimenter bias caused by non-conscious observation of patterns in the data was prevented by recoding the tapes halfway through the study. Only after all data had been collected were the codes broken. After 20 min, a different tape with seaside sounds was played to all patients for the remainder of the
operation. Anaesthesia was induced with thiopentone and droperidol, and atracurium or pancuronium was used for muscle relaxation. Maintenance took place with 66% nitrous oxide in oxygen, supplemented with sufentanil or fentanyl. Each patient was interviewed as soon as possible after surgery (mean interval between start of second tape and postoperative testing 81 min, range 30-179). Patients were asked about any recall
of intraoperative events. They were then invited to name the first three examples of of a non-experimental category "vegetables" and the experimental categories "fruit" and "colours" that came to mind. Any cited word corresponding to one of those presented during anaesthesia was scored at a "hit". A maximum of four hits could thus be obtained. A one-tailed Student’s t-test was carried out to determine whether the groups differed in the number of hits. There were no significant differences between the groups with respect to age, duration of surgery, preoperative anxiety and number of previous operations. No patient recalled intraoperative events. The mean (SEM) number of hits for the experimental group was 2-4 (0-18) and for the control group 1 ’84 (0-2) (t = 2-8, df=48, p < 0025). There was no significant difference between groups with respect to the non-experimental category "vegetables". The results suggest that even neutral auditory stimuli are registered in the anaesthetised cortex. Our findings accord with Roorda-Hrdlickova and colleagues,4 who used a different anaesthetic technique. In that study anaesthesia was induced with propofol and maintained with nitrous oxide in oxygen and isoflurane. It is, therefore, unlikely that auditory informationprocessing is restricted to rare occasions or particular anaesthetic cocktails. We seem to be "just scratching the surface of this important issue", as Millers put it. Unconscious perception of auditory stimuli during general anaesthesia has substantial implications. Inappropriate or ambiguous remarks "overheard" during surgery may lead to psychological disturbances or delayed postoperative recovery6. It has therefore been suggested that anaesthetised patients should be provided with earplugs.7,8 We recommend instead the use of therapeutic suggestions during anaesthesia, which may have a beneficial effect on the postoperative course.9 We thank the
patients who participated in this study, the departments of anaesthesia, general surgery, and plastic and reconstructive surgery at the St Lucas Hospital, Amsterdam, Dr J. N. Keeman, Prof J. G. Bovill, Prof J. G. Jones, and Prof K. Millar. Department of Medical Psychology and Psychotherapy, Erasmus University, 3000 DR Rotterdam, Netherlands
M. JELICIC B. BONKE
Department of Anaesthesia, Hospital, Amsterdam
D. K. APPELBOOM
St Lucas
1. Editorial. Advertising dunng anaesthesia? Lancet 1986; ii: 1019-20. 2. Bonke B, Fitch W, Millar K, eds. Memory and awareness in anaesthesia. Amsterdam: Swets & Zeitlinger, 1990. 3. Wilson ME, Spiegelhalter D. Awareness during anaesthesia. Lancet 1986; ii: 1338 4. Roorda-Hrdličková V, Wolters G, Bonke B, Phaf RH Unconscious perception during general anaesthesia, demonstrated by an implicit memory task. In: Bonke B, Fitch W, Millar K, eds. Memory and awareness in anaesthesia. Amsterdam: Swets & Zeitlinger, 1990: 150-55. 5. Miller RD, ed The year book of anesthesia. Chicago. Year Book Medical Publishers
Inc, 1989: 7-9
awakening paralyzed during surgery. A syndrome of traumatic JAMA 1975; 234: 67-68. 7. Scott DL. Awareness during general anaesthesia. Can Anaesth Soc J 1972; 19: 173-83. 8. Davis R. Anaesthesia, amnesia, dreams and awareness. Med J Aust 1987; 146: 4-5. 9. Evans C, Richardson PH. Improved recovery and reduced postoperative stay after therapeutic suggestions during general anaesthesia. Lancet 1988; ii 491-93. 6. Blacher RS. On neurosis.
LCAT activity
as a
prognostic liver function test
SIR,-Assessment of liver function depends on crude measures of synthetic capability (albumin, prothrombin time), hepatocyte damage (aminotransferases), and cholestasis (bilirubin). Although such measures provide information about the immediate functional state of the liver, they are rarely useful in the prediction of outcome of liver disease, and only serum bilirubin is accepted as having a prognostic role for patients with primary biliary cirrhosis.1 However, accurate prediction of prognosis is important in decisions about orthotopic liver transplantation. Are there other, more specific measures of liver function that may prove useful in the determination of outcome? Lecithin cholesterol acyltransferase (LCAT, EC 2.3.1.43) catalyses the esterification of cholesterol in plasma, is synthesised predominantly by the liver, and is a sensitive measure of liver
250
Endoscopic correction of primary vesicoureteric reflux SIR,-Mr Puri (June 2, p 1320) describes a simple and effective technique (about whose long-term effects we have greater reservations than he) for the abolition of the radiological appearance of vesicoureteric reflux (VUR), but he does not discuss its benefit to
patients. In particular, we would like to have evidence of a causal association between VUR and morbidity and to know how effectively such intervention may reduce the reflux. We also question the wisdom of the adoption of a data-collection protocol in which the subjects (mainly girls) would have annual micturating cystouretheography for up to five years. Paediatric Department, Southmead Hospital, Bristol BS10 5NB, UK
*** This letter has been shown - ED. L.
Modified Child - Pugh Class
Plasma LCAT activity measured by proteoliposome method in healthy controls and cirrhotic patients. Horizontal bars=mean, vertical bars=SEM.
function.2,3 We used the proteoliposome method4 to measure plasma LCAT activity in 28 patients with histologically confirmed cirrhotic liver disease (16 with alcoholic cirrhosis; 7 primary biliary cirrhosis; 5 cryptogenic cirrhosis) and 20 healthy volunteers. This method uses a well-defined exogenous substrate; it does not have the inaccuracies of other techniques;2,3 and the values obtained are closely related to LCAT concentration.5 We found a clear difference between the LCAT activities of healthy subjects and patients (mean 119.0 [SEM 84] 39-8 [53] nmol/ml per hour; p < 0-001) with normal values in only 2 patients. Moreover, LCAT activity significantly correlated with modified Child-Pugh scores (by linear regression r = - 0-483; p=0011; figure) indicating that it may be a powerful additional test for the precise definition of severity and outcome of liver disease. Plasma LCAT activity has been reported as a predictor of early allograft function in transplant recipients6 and of viability of allograft donors. We now propose incorporation of LCAT measurement into models assessing the best timing for liver transplantation, especially since previous models have so far failed to offer any useful clinical application.8 Hepato-biliary and Liver Transplantation Unit, Royal Free Hospital,
RICHARD C. HORTON
London NW3 2QG, UK
JAMES S. OWEN
Rydning A, Schrumdf E, Abdelnoor M, Elgjo K, Jenssen E. Factors of prognostic importance in primary biliary cirrhosis. Scand J Gastroenterol 1990; 25: 119-26. 2. Martiis MD, Barlattani A, Parenzi A, Sebastiani F. Pattern of LCAT activity m the course of liver cirrhosis. J Int Med Res 1983; 11: 232-38. 3. Simko V, Kelley RE, Dincsoy HP. Predicting severity of liver disease: twelve laboratory tests evaluated by multiple regression. J Int Med Res 1985; 13: 249-54. 4. Chen C, Albers JJ. Characterisation of proteoliposomes containing apoprotein A1: a new substrate for the measurement of lecithin: cholesterol acyltransferase activity. J Lipid Res 1982; 23: 680-91. 5. Floren CH, Chen C-H, Franzen J, Albers JJ. Lecithin: cholesterol acyltransferase m liver disease. Scand J Clin Lab Invest 1987; 47: 613-17. 6. Shimada M, Yanaga K, Makowka L, Kakizoe S, van Thiel DH, Starzl TE. Significance of LCAT activity as a prognostic indicator of early allograft function in clinical liver transplantation. Transplantation 1989; 48: 600-03. 7. Higashi H, Yanaga K, Shimada M, Makowka L, van Thiel DH, Starzl TE. Plasma LCAT activity in multiple organ donors: a predictor of allograft viability in clinical liver transplantation. Transplantation Proc 1990; 22: 433-34. 8. Keiding S, Ericzon BG, Eriksson S, et al. Survival after liver transplantation of patients with primary biliary cirrhosis in the Nordic countries Scand J 1.
Gastroenterol 1990; 25: 11-18.
T. L. CHAMBERS
J. D. FRANK
to
Mr Puri, whose
reply follows.
SiR,—The management of vesicoureteric reflux in children has been very controversial. During the past three decades there have been over 5000 reports on this subject. The Birmingham Reflux Study is probably the best known of the studies that prospectively compared medical and surgical management of vesicoureteric reflux. This study showed that more than half the patients continued to show severe reflux after five years of medical treatment. What is to be done for these patients? Should they have a simple effective day-care procedure to stop reflux or should they embark on a lifetime of chemoprophylaxis? My investigation was not designed to address all aspects of vesicoureteric reflux-it was merely intended as a contribution to the controversy. With respect to the "annual" micturating cystourethrography, we initially closely monitored the results of this new procedure, but with further experience now do micturating cystourethrography at three months, at one year, and again at three years after endoscopic correction of reflux. The Birmingham Reflux Study Group who treat patients by chemoprophylaxis do micturating cystography at two years and five years. If reflux persists then presumably they go on
investigating.
Children’s Research Centre, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland 1.
PREM PURI
Birmingham Reflux Study Group. Prospective trial of operative versus nonoperative treatment of severe vesicoureteric reflux in children: five years observation. Br Med J 1987; 295: 237-41.
Non-coronary thrombolysis SIR,-We read with interest your editorial concerning noncoronary thrombolysis (March 24, p 691). This technique for the treatment of acute vascular ischaemia is one in which our unit has considerable experience. Whilst endorsing most of what was said, we would like to make some additional points. Not enough emphasis was placed on the use of recombinant tissue plasminogen activator (alteplase, r-TPA). Although individual series with r-TPA have not yet accrued sufficient numbers to reach statistical significance, without exception they show results superior to streptokinase treatment." Lysis times are shorter, limb loss and mortality rates lower, and thrombus specificity leads to less interference with the systemic haemostatic system and so to fewer haemorrhagic complications. We now use r-TPA as the agent of choice. Rethrombosis was cited in the editorial as a substantial problem. Our results have been encouraging in that three cases of rethrombosis after initial lysis have been re-cleared with r-TPA. Streptokinase cannot be used again in this context because of
possible allergic complications. We agree that if lysis is not well established by 12 h then thrombolysis is unlikely to succeed at that dose. However, the doses of r-TPA used in the UK (05 mg/h)’ are considerably less than