1297
SiR,—In view of the inaccuracy of the clinical diagnosis of DVT PE, it is surprising that only 83% of patients analysed in the British Thomcic Society’s study underwent investigations to attempt to objectively confirm a clinical suspicion of venous thrombo-embolism before anticoagulation. Furthermore, objective confirmation of a clinical suspicion of failure or recurrence was sought in only 42% of patients. Although not an objective of the study, since 4-9% of patients had complications of anticoagulation (including one death) is it reasonable to initiate or prolong or
U/1, and no effect of treatment delay on infarct size was recorded. Thus, very early treatment with intravenous alteplase results in a substantial (30-70%) reduction of infarct size. More than half this effect is lost when treatment is delayed by more than 60-75 min. These results emphasise the importance of finding strategies for
pre-hospital thrombolysis.4
anticoagulation therapy on the basis of a clinical suspicion of venous
Cardiovascular Research Institute Maastricht, PO box 616, University of Limburg, 6200 Maastricht, Netherlands; and Thoraxcentre,
thrombo-embolism without objective confirmation?
University Hospital Dijkzigt,
Division of Medicine, M.D Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA
Rotterdam 1. Van der Werf
JOHN SEYMOUR
Effect of thrombolytic treatment delay on myocardial infarct size SIR,-Intravenous thrombolytic therapy is now given routinely in patients with acute myocardial infarction (AMI). In large trials survival seemed better in patients treated early, and many hospitals restrict therapy to those presenting within 6 h after first symptoms. However, the effect of treatment delay on survival is not pronounced and Dr White (July 25, p 221) has advocated extension of this time limit. Measurement of infarct size allows more detailed analysis of the effect of treatment delay in thrombolytic therapy, since quantitative estimates can easily be obtained in more than 95% of patients. In three randomised trials of thrombolytic therapyl-3 by the European Cooperative Study Group, infarct size was calculated as the cumulative activity of myocardial a-hydroxybutyrate dehydrogenase released per litre of plasma during the first 72 h after AMI (Q). 1374 patients with AMI were allocated to treatment with alteplase (single chain, Boehringer Ingelheim, Germany) within 6 h of first symptoms. Alteplase was given as a 10 mg bolus, followed by 50 mg infused over the first hour and 20 mg/h over the next 2 h. All patients received aspirin. Median infarct size (95 % CI) calculated in 1334 patients (97%), was 666 U/I (591-736). The figure shows the effect of treatment delay on infarct size. Overall linear regression analysis demonstrated a significant (p < 0-001) effect of treatment delay on infarct size: Qn 584 + 65 (treatment delay) U/1. However, additional benefit of very early treatment is apparent and deviation of linearity was significant. In 61 patients treated within 75 min, median infarct size was 331 (258-602) U/1 and, within this group, no longer related to delay in treatment. In the remaining 1272 patients, a linear relation =
persisted: Q = 685 + 56 (treatment delay) U/I (p 0-0001). In 353 placebo-treated patients,! median infarct size was 867 (779-933) =
Median infarct size
Treatment
F, Arnold AER, for the ECSG. Intravenous tissue plasminogen activator and size of infarct, left ventricular function and survival in acute myocardial infarction. BMJ 1988; 297: 1374-79. 2. Simoons ML, Arnold AER, Betriu A, et al. Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty. Lancet 1988; i: 197-203. 3. De Bono DP, Simoons ML, Tijssen J, et al. Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind ECSG trial. Br Heart J 1992; 67: 122-28. 4. Bouten MJM, Simoons ML Strategies for pre-hospital thrombolysis: an overview. Eur Heart J 1991; 12 (suppl G): 39-42.
Reverse passive haemagglutination test for identification and serotyping of polioviruses SIR,-The identification of poliovirus by the neutralisation test is laborious, so we have developed a simple and rapid reverse passive haemagglutination (RPHA) test. 40 stool specimens were obtained from immunised infants 1 week after oral poliomyelitis vaccination. Polioviruses were isolated on Vero cells and identified by standard methods. Mouse monoclonal antibodies Mah4e (anti-poliovirus type 1), S2-16 (anti-poliovirus 2), and SuWa (anti-poliovirus 3) were used to coat sheep red blood cells (SRBC) (SRBC-Mah4e, SRBC-S3-16, and SRBC-SuWa).2 SRBC were fixed with 0-5% glutaraldehyde at room temperature for 1 h and washed with phosphate-buffered saline (PBS). The fixed SRBC were treated with tannic acid (30 µl/ml) at 37°C for 10 min. After washing with saline, a 6-0% suspension of the tanninised SRBC was prepared in Mcllvain buffer containing 0-5 mol/1 NaCI (pH 5-0) and mixed with an equal volume of poliovirus monoclonal antibody which was purified by 33-3% saturated ammonium sulphate (50 µg/ml) from immunised BALB/c mouse ascites with antibody-producing hybridoma. The mixture was incubated at room temperature for 1 h to prepare antibody-sensitised SRBC. The SRBC was washed with PBS, and a 0-6% suspension was prepared in PBS containing 20% heat-inactivated rabbit serum (PBS-RS). The monoclonal antibodies reacted with both vaccine and wild strains of homologous serotype by enzyme-linked immunosorbent assay. The RPHA test was by microtitration on plates with 120 V-shaped wells. Culture fluid of inoculated stool samples that were cytopathic on Vero cells were used as specimens for the RPHA test. Serial two-fold dilutions of the specimens were made in triplicate with a 25 III loop and a diluent of PBS-RS containing 1-0% SRBC. SRBC-Mah4e, SRBC-S2-16, and SRBC-SuWa were added to the lst, 2nd, and 3rd dilution series, respectively. After shaking, the microtitration plate was covered and kept at room temperature for 1 h, and agglutination (poliovirus positive) was observed by eye. The sensitivity of the RPHA test for poliovirus was estimated by the tissue-culture infective dose5o (TCID5o)’ SRBC coated with type-specific monoclonal antibody caused agglutination with the homologous poliovirus only. TCID per 50 gl was 106-04 for SRBC-Mah4e, 10561 for SRBC-S2-16, and 10585 for SRBC-SuWa. Thus RPHA is sensitive for poliovirus detection. No false negative or positive reactions occurred: No of samples RPHA typing Neutralisation type
delay (hours)
Effect of delay of thrombolytic treatment on infarct size. No of patients shown at top of each column Columns=means, vertical bars = 95% C I
W. TH. HERMENS G. M. WILLEMS K. M. NIJSSEN M. L. SIMOONS, for the European Cooperative Study Group
Although the numbers examined were small, the RPHA test was useful and practicable for the identification of poliovirus. SRBC coated with type-specific monoclonal antibody gave no non-specific
1298
agglutination, and sensitivity was maintained even after 6 months’ storage at 4°C. These three monoclonal antibodies reacted with all wild-type strains which is why we used them in the preparation of antibody-sensitised SRBC. Since we have not tested all wild-type strains, we cannot exclude the possibility that the RPHA test might miss some wild-type strains. However, if the neutralisation test detected some strains that were not detected by RPHA, a modified antibody-sensitised SRBC could be prepared for its detection. The RPHA test is simple, sensitive, and less time-consuming than with other poliovirus tests. Department of Veterinary Microbiology, University, Tottori, Japan; Department of Enterovirus, National Institute of Health, Tokyo; Department of Microbiology,
Tottori
Tottori Prefectural Public Health Laboratories, and Department of Virology, Noguchi Memorial Institute for Medical Research, Legon, Ghana
TAKESHI SANEKATA MINEO ARITA AYUMI KAWAMOTO ALBERT FLANK MAGNUSEN
poliomyelitis eradication by the year 2000; manual for the virological investigation of poliomyelitis. Geneva: World Health Organization, 1989. 2. Sanekata T, Okada H. Human rotavirus detection by agglutination of antibody coated erythrocytes. J Clin Microbiol 1983; 17: 1141-47. 1. Global
Acute renal failure after overdose of colloidal bismuth subcitrate SIR,-A 21-year-oid man was admitted 3 h atter ingesting thirty-nine (4-68 g) tablets of bismuth subcitrate. Emesis was induced within 2 h. On admission he showed no encephalopathy, was not clinically dehydrated, pulse was 80 per min, blood pressure 118/75 mm Hg, and he had epigastric pain. Gastric lavage was not done. Biochemistry was normal but he had a neutrophil leucocytosis (white-cells 14-2 x 109, 69% neutrophils.) He was prescribed intravenous crystalloid infusion but over the next 48 h urinary output fell and renal function deteriorated. 3 days later he was transferred to the renal unit. Admission creatinine was 342 umol/1 and the patient had slightly increased aspartate aminotransferase (56 IU/1), alanine aminotransferase (95 IU/1), and lactate dehydrogenase (2200 IU/1). 24 h urinary N-acetylglucosaminidase was increased at 38-4 U (normal 2-77-7-85). Renal biopsy at 4 days revealed moderate acute tubular necrosis with focally prominent regenerative atypia; no bismuth was detected in the biopsy specimen. He was managed with intravenous frusemide, dopamine, mannitol, and crystalloids. Creatinine peaked at 420 µmol/l and renal function gradually returned to normal (figure). He was discharged well on day 120. Serum bismuth was estimated by inductively coupled plasma mass spectrometry (ICP-MS). Chronic toxicity resulting in encephalopathyl,2 and acute toxicity leading to nephrotoxicity3-5 have been documented with a variety of bismuth salts. Colloidal bismuth has a higher risk than other salts because of higher bioavailabihty.1 Therapeutic doses give bismuth concentrations of 10-20 µg/l which are not toxic. An alerting level of 50 µg/1 has been suggested.
There have been two reports of acute renal failure after overdose with colloidal bismuth. A 27-year-old man, bismuth concentration not recorded, recovered after colonic purgation and haemodialysis.s A 76-year-old man, bismuth concentration 1600 µg/l, died from a perforated duodenal ulcer. His kidneys contained bismuth at 11 mg/g and 16 mg/g.5 In our patient serum bismuth fell rapidly in the first few hours due to distribution. Whole blood and plasma concentrations should be monitored in such cases. Although ICP-MS is not commonly available, bismuth may be measured by atomic absorption spectrophotometry with hydride generationThe mechanism by which high concentrations of bismuth cause nephrotoxicity is not clear and the management of bismuth overdose is still being developed. Haemodialysis may be necessary in acute renal failure but has little effect upon the rate of elimination from the intracellular compartment in which bismuth has a long half-life. In the very early stages chelating agents may be beneficial; the current favoured treatment is mercapto-1-propane sulphonic acid.2,8 Department of Medicine, Hospital, Oban, Argyll, Department of Renal Medicine and Institute of Biochemistry, Royal Infirmary, Glasgow G4 0SF, UK Oban County
F. HUWEZ A. PALL D. LYONS M. J. STEWART
Martin-Bouyer G. Intoxications par les sels de bismuth administre par voie orale; enquete epidemiologique. Therapie 1976; 31: 683-702. 2. Playford RJ, Matthews CH, Campbell MA, et al. Bismuth-induced encephalopathy associated caused by tripotassium dicitratobismuthate in a patient with chronic 1.
renal failure. Gut 1990; 31: 359-60. 3. Randall RE, Osterhoff RJ, Bakerman S, Setter JG. Bismuth nephrotoxicity. Ann Intern Med 1972; 77: 481-82. 4. Hudson M, Mowat NAG. Reversible toxicity in poisoning with colloidal bismuth subcitrate. BMJ 1989; 229: 159. 5. Taylor EG, Klenerman P. Acute renal failure after colloidal bismuth subcitrate after overdose. Lancet 1990; 335: 670-71. 6. Lee SP. Study on the absorption and excretion of tripotassium dicitratobismuthate in man. Res Commun Chem Pathol 1981; 34: 359-64. 7. Froomes PA, Wan AT, Harrison PM, McLean AJ. Improved assay for bismuth in biological samples by atomic absorption spectrophotometry with hydride generation. Clin Chem 1988; 34: 382-84. 8. Aaseth J. Recent advances in the therapy of metal poisonings with chelating agents Hum Toxicol 1983; 2: 257-72.
The Leicester anti-vaccination movement SIR,-Professor Swales (Oct 24, p 1019) is as concerned with the
politics of conscientious objection at the end of the 19th century as he is with the epidemiology of smallpox and vaccinia. He writes, "Fortunately, Leicester was spared the epidemic confidently predicted by The Lancet ... ".The town’s escape is attributed to the Leicester method of quarantine and disinfection, and to vaccination in surrounding areas of the country. My father, Dr James Eddy, was a general practitioner in Leicester for the first forty years of this century. During that time, as Swales shows, there was continuing resistance to vaccination and a low vaccination rate. Throughout that period there were occasional notifications of smallpox, with a low morbidity and negligible mortality. These were, of course, alastrim or varola minor. The medical officer of health at that time, Dr Killick Millard, believed that there was a continuing epidemic of variola minor which conferred a lasting immunity to classic Asian, or old-world, smallpox, variola major, should that virulent infection arrive. To let alastrim run, with some control by notification and isolation, was preferable to, and more effective than, unpopular compulsory general vaccination. I remember that my father notified occasional cases of smallpox in his practice. He had seen virulent variola major in London and thought that anti-vaccinationists were fools. "This mild form of smallpox", he said "is bringing the disease into
contempt". Is it not possible that the replacement of virulent old-world Asian smallpox by non-fatal alastrim may have protected Leicester? From Bigg’s table, cited by Swales, something other than vaccination happened abruptly from 1873 onwards.
Days after ingestion Serum creatinine ([]-[]), and bismuth (0---0).
serum
(•-•)
and blood
33 Brunswick St West, Hove, East Sussex BN3 1EL, UK
T.P.EDDY
SiR,—In view of the inaccuracy of the clinical diagnosis of DVT PE, it is surprising that only 83% of patients analysed in the British Thomcic Society’s study underwent investigations to attempt to objectively confirm a clinical suspicion of venous thrombo-embolism before anticoagulation. Furthermore, objective confirmation of a clinical suspicion of failure or recurrence was sought in only 42% of patients. Although not an objective of the study, since 4-9% of patients had complications of anticoagulation (including one death) is it reasonable to initiate or prolong or
U/1, and no effect of treatment delay on infarct size was recorded. Thus, very early treatment with intravenous alteplase results in a substantial (30-70%) reduction of infarct size. More than half this effect is lost when treatment is delayed by more than 60-75 min. These results emphasise the importance of finding strategies for
pre-hospital thrombolysis.4
anticoagulation therapy on the basis of a clinical suspicion of venous
Cardiovascular Research Institute Maastricht, PO box 616, University of Limburg, 6200 Maastricht, Netherlands; and Thoraxcentre,
thrombo-embolism without objective confirmation?
University Hospital Dijkzigt,
Division of Medicine, M.D Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA
Rotterdam 1. Van der Werf
JOHN SEYMOUR
Effect of thrombolytic treatment delay on myocardial infarct size SIR,-Intravenous thrombolytic therapy is now given routinely in patients with acute myocardial infarction (AMI). In large trials survival seemed better in patients treated early, and many hospitals restrict therapy to those presenting within 6 h after first symptoms. However, the effect of treatment delay on survival is not pronounced and Dr White (July 25, p 221) has advocated extension of this time limit. Measurement of infarct size allows more detailed analysis of the effect of treatment delay in thrombolytic therapy, since quantitative estimates can easily be obtained in more than 95% of patients. In three randomised trials of thrombolytic therapyl-3 by the European Cooperative Study Group, infarct size was calculated as the cumulative activity of myocardial a-hydroxybutyrate dehydrogenase released per litre of plasma during the first 72 h after AMI (Q). 1374 patients with AMI were allocated to treatment with alteplase (single chain, Boehringer Ingelheim, Germany) within 6 h of first symptoms. Alteplase was given as a 10 mg bolus, followed by 50 mg infused over the first hour and 20 mg/h over the next 2 h. All patients received aspirin. Median infarct size (95 % CI) calculated in 1334 patients (97%), was 666 U/I (591-736). The figure shows the effect of treatment delay on infarct size. Overall linear regression analysis demonstrated a significant (p < 0-001) effect of treatment delay on infarct size: Qn 584 + 65 (treatment delay) U/1. However, additional benefit of very early treatment is apparent and deviation of linearity was significant. In 61 patients treated within 75 min, median infarct size was 331 (258-602) U/1 and, within this group, no longer related to delay in treatment. In the remaining 1272 patients, a linear relation =
persisted: Q = 685 + 56 (treatment delay) U/I (p 0-0001). In 353 placebo-treated patients,! median infarct size was 867 (779-933) =
Median infarct size
Treatment
F, Arnold AER, for the ECSG. Intravenous tissue plasminogen activator and size of infarct, left ventricular function and survival in acute myocardial infarction. BMJ 1988; 297: 1374-79. 2. Simoons ML, Arnold AER, Betriu A, et al. Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty. Lancet 1988; i: 197-203. 3. De Bono DP, Simoons ML, Tijssen J, et al. Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind ECSG trial. Br Heart J 1992; 67: 122-28. 4. Bouten MJM, Simoons ML Strategies for pre-hospital thrombolysis: an overview. Eur Heart J 1991; 12 (suppl G): 39-42.
Reverse passive haemagglutination test for identification and serotyping of polioviruses SIR,-The identification of poliovirus by the neutralisation test is laborious, so we have developed a simple and rapid reverse passive haemagglutination (RPHA) test. 40 stool specimens were obtained from immunised infants 1 week after oral poliomyelitis vaccination. Polioviruses were isolated on Vero cells and identified by standard methods. Mouse monoclonal antibodies Mah4e (anti-poliovirus type 1), S2-16 (anti-poliovirus 2), and SuWa (anti-poliovirus 3) were used to coat sheep red blood cells (SRBC) (SRBC-Mah4e, SRBC-S3-16, and SRBC-SuWa).2 SRBC were fixed with 0-5% glutaraldehyde at room temperature for 1 h and washed with phosphate-buffered saline (PBS). The fixed SRBC were treated with tannic acid (30 µl/ml) at 37°C for 10 min. After washing with saline, a 6-0% suspension of the tanninised SRBC was prepared in Mcllvain buffer containing 0-5 mol/1 NaCI (pH 5-0) and mixed with an equal volume of poliovirus monoclonal antibody which was purified by 33-3% saturated ammonium sulphate (50 µg/ml) from immunised BALB/c mouse ascites with antibody-producing hybridoma. The mixture was incubated at room temperature for 1 h to prepare antibody-sensitised SRBC. The SRBC was washed with PBS, and a 0-6% suspension was prepared in PBS containing 20% heat-inactivated rabbit serum (PBS-RS). The monoclonal antibodies reacted with both vaccine and wild strains of homologous serotype by enzyme-linked immunosorbent assay. The RPHA test was by microtitration on plates with 120 V-shaped wells. Culture fluid of inoculated stool samples that were cytopathic on Vero cells were used as specimens for the RPHA test. Serial two-fold dilutions of the specimens were made in triplicate with a 25 III loop and a diluent of PBS-RS containing 1-0% SRBC. SRBC-Mah4e, SRBC-S2-16, and SRBC-SuWa were added to the lst, 2nd, and 3rd dilution series, respectively. After shaking, the microtitration plate was covered and kept at room temperature for 1 h, and agglutination (poliovirus positive) was observed by eye. The sensitivity of the RPHA test for poliovirus was estimated by the tissue-culture infective dose5o (TCID5o)’ SRBC coated with type-specific monoclonal antibody caused agglutination with the homologous poliovirus only. TCID per 50 gl was 106-04 for SRBC-Mah4e, 10561 for SRBC-S2-16, and 10585 for SRBC-SuWa. Thus RPHA is sensitive for poliovirus detection. No false negative or positive reactions occurred: No of samples RPHA typing Neutralisation type
delay (hours)
Effect of delay of thrombolytic treatment on infarct size. No of patients shown at top of each column Columns=means, vertical bars = 95% C I
W. TH. HERMENS G. M. WILLEMS K. M. NIJSSEN M. L. SIMOONS, for the European Cooperative Study Group
Although the numbers examined were small, the RPHA test was useful and practicable for the identification of poliovirus. SRBC coated with type-specific monoclonal antibody gave no non-specific
1298
agglutination, and sensitivity was maintained even after 6 months’ storage at 4°C. These three monoclonal antibodies reacted with all wild-type strains which is why we used them in the preparation of antibody-sensitised SRBC. Since we have not tested all wild-type strains, we cannot exclude the possibility that the RPHA test might miss some wild-type strains. However, if the neutralisation test detected some strains that were not detected by RPHA, a modified antibody-sensitised SRBC could be prepared for its detection. The RPHA test is simple, sensitive, and less time-consuming than with other poliovirus tests. Department of Veterinary Microbiology, University, Tottori, Japan; Department of Enterovirus, National Institute of Health, Tokyo; Department of Microbiology,
Tottori
Tottori Prefectural Public Health Laboratories, and Department of Virology, Noguchi Memorial Institute for Medical Research, Legon, Ghana
TAKESHI SANEKATA MINEO ARITA AYUMI KAWAMOTO ALBERT FLANK MAGNUSEN
poliomyelitis eradication by the year 2000; manual for the virological investigation of poliomyelitis. Geneva: World Health Organization, 1989. 2. Sanekata T, Okada H. Human rotavirus detection by agglutination of antibody coated erythrocytes. J Clin Microbiol 1983; 17: 1141-47. 1. Global
Acute renal failure after overdose of colloidal bismuth subcitrate SIR,-A 21-year-oid man was admitted 3 h atter ingesting thirty-nine (4-68 g) tablets of bismuth subcitrate. Emesis was induced within 2 h. On admission he showed no encephalopathy, was not clinically dehydrated, pulse was 80 per min, blood pressure 118/75 mm Hg, and he had epigastric pain. Gastric lavage was not done. Biochemistry was normal but he had a neutrophil leucocytosis (white-cells 14-2 x 109, 69% neutrophils.) He was prescribed intravenous crystalloid infusion but over the next 48 h urinary output fell and renal function deteriorated. 3 days later he was transferred to the renal unit. Admission creatinine was 342 umol/1 and the patient had slightly increased aspartate aminotransferase (56 IU/1), alanine aminotransferase (95 IU/1), and lactate dehydrogenase (2200 IU/1). 24 h urinary N-acetylglucosaminidase was increased at 38-4 U (normal 2-77-7-85). Renal biopsy at 4 days revealed moderate acute tubular necrosis with focally prominent regenerative atypia; no bismuth was detected in the biopsy specimen. He was managed with intravenous frusemide, dopamine, mannitol, and crystalloids. Creatinine peaked at 420 µmol/l and renal function gradually returned to normal (figure). He was discharged well on day 120. Serum bismuth was estimated by inductively coupled plasma mass spectrometry (ICP-MS). Chronic toxicity resulting in encephalopathyl,2 and acute toxicity leading to nephrotoxicity3-5 have been documented with a variety of bismuth salts. Colloidal bismuth has a higher risk than other salts because of higher bioavailabihty.1 Therapeutic doses give bismuth concentrations of 10-20 µg/l which are not toxic. An alerting level of 50 µg/1 has been suggested.
There have been two reports of acute renal failure after overdose with colloidal bismuth. A 27-year-old man, bismuth concentration not recorded, recovered after colonic purgation and haemodialysis.s A 76-year-old man, bismuth concentration 1600 µg/l, died from a perforated duodenal ulcer. His kidneys contained bismuth at 11 mg/g and 16 mg/g.5 In our patient serum bismuth fell rapidly in the first few hours due to distribution. Whole blood and plasma concentrations should be monitored in such cases. Although ICP-MS is not commonly available, bismuth may be measured by atomic absorption spectrophotometry with hydride generationThe mechanism by which high concentrations of bismuth cause nephrotoxicity is not clear and the management of bismuth overdose is still being developed. Haemodialysis may be necessary in acute renal failure but has little effect upon the rate of elimination from the intracellular compartment in which bismuth has a long half-life. In the very early stages chelating agents may be beneficial; the current favoured treatment is mercapto-1-propane sulphonic acid.2,8 Department of Medicine, Hospital, Oban, Argyll, Department of Renal Medicine and Institute of Biochemistry, Royal Infirmary, Glasgow G4 0SF, UK Oban County
F. HUWEZ A. PALL D. LYONS M. J. STEWART
Martin-Bouyer G. Intoxications par les sels de bismuth administre par voie orale; enquete epidemiologique. Therapie 1976; 31: 683-702. 2. Playford RJ, Matthews CH, Campbell MA, et al. Bismuth-induced encephalopathy associated caused by tripotassium dicitratobismuthate in a patient with chronic 1.
renal failure. Gut 1990; 31: 359-60. 3. Randall RE, Osterhoff RJ, Bakerman S, Setter JG. Bismuth nephrotoxicity. Ann Intern Med 1972; 77: 481-82. 4. Hudson M, Mowat NAG. Reversible toxicity in poisoning with colloidal bismuth subcitrate. BMJ 1989; 229: 159. 5. Taylor EG, Klenerman P. Acute renal failure after colloidal bismuth subcitrate after overdose. Lancet 1990; 335: 670-71. 6. Lee SP. Study on the absorption and excretion of tripotassium dicitratobismuthate in man. Res Commun Chem Pathol 1981; 34: 359-64. 7. Froomes PA, Wan AT, Harrison PM, McLean AJ. Improved assay for bismuth in biological samples by atomic absorption spectrophotometry with hydride generation. Clin Chem 1988; 34: 382-84. 8. Aaseth J. Recent advances in the therapy of metal poisonings with chelating agents Hum Toxicol 1983; 2: 257-72.
The Leicester anti-vaccination movement SIR,-Professor Swales (Oct 24, p 1019) is as concerned with the
politics of conscientious objection at the end of the 19th century as he is with the epidemiology of smallpox and vaccinia. He writes, "Fortunately, Leicester was spared the epidemic confidently predicted by The Lancet ... ".The town’s escape is attributed to the Leicester method of quarantine and disinfection, and to vaccination in surrounding areas of the country. My father, Dr James Eddy, was a general practitioner in Leicester for the first forty years of this century. During that time, as Swales shows, there was continuing resistance to vaccination and a low vaccination rate. Throughout that period there were occasional notifications of smallpox, with a low morbidity and negligible mortality. These were, of course, alastrim or varola minor. The medical officer of health at that time, Dr Killick Millard, believed that there was a continuing epidemic of variola minor which conferred a lasting immunity to classic Asian, or old-world, smallpox, variola major, should that virulent infection arrive. To let alastrim run, with some control by notification and isolation, was preferable to, and more effective than, unpopular compulsory general vaccination. I remember that my father notified occasional cases of smallpox in his practice. He had seen virulent variola major in London and thought that anti-vaccinationists were fools. "This mild form of smallpox", he said "is bringing the disease into
contempt". Is it not possible that the replacement of virulent old-world Asian smallpox by non-fatal alastrim may have protected Leicester? From Bigg’s table, cited by Swales, something other than vaccination happened abruptly from 1873 onwards.
Days after ingestion Serum creatinine ([]-[]), and bismuth (0---0).
serum
(•-•)
and blood
33 Brunswick St West, Hove, East Sussex BN3 1EL, UK
T.P.EDDY
