- Email: [email protected]
Sensitivity of serological assays to identify blood donors with hepatitis C viraemia
1018
chromosomes in controls to 1 of 106 (0-9%) in cases (r’=119, p < 0-001). The excess of CYP2D6B alleles among patients with Parkinson’s disease was almost entirely accounted for by a doubled frequency of the wt/CYP2D6B genotype compared with controls (37-7% 18-1%). The numbers studied were too small to detect any changes in homozygous PM frequency (2 in both groups), and we did not attempt to identify the rare CYP2D6C allele, also associated with deficient CYP2D6-mediated metabolism.9 How might the hepatic CYP2D6 isozyme influence the onset of Parkinson’s disease? Apart from a possible role in environmental neurotoxin inactivation, recent evidence indicates that the gene product may influence brain function. A partial cDNA with 100% sequence homology to CYP2D6 has recently been cloned from the caudate nucleus in man, to and CYP2D6-like metabolic activity is distributed throughout the canine brain; this protein has an affinity for drugs that interact with the neuronal dopamine transporter. to Individuals homozygous or heterozygous for CYP2D6 mutations may therefore have lower rates of CYP2D6-mediated chemical metabolism in the brain and altered dopamine homoeostasis. In this preliminary study we found that the commonest genotype to confer impaired debrisoquine metabolism, wt/CYP2D6B, is twice as common among patients with Parkinson’s disease than in the normal population. These findings would not be influenced by concomitant drug therapy. However, we did not observe any overall increase in the total number of mutant alleles among parkinsonian patients and it is possible that a specific genetic mechanism, such as linkage disequilibrium, underlies the apparent association between Parkinson’s disease and the CYP2D6B allele, or indeed that the findings of this small pilot study, with controls matched for ethnicity alone, could be explained by chance. Larger controlled studies, perhaps with an emphasis on patients with early onset of Parkinson’s
disease, are now required. We thank Dr R. G. Cooper and Dr D. Bates for assistance in recruitment and Dr N. Caporaso for statistical advice. Supported Wellcome Trust, BAT Ltd, and Bayer UK plc.
patient by the
REFERENCES 1. Calne DB, Langston JW. Aetiology of Parkinson’s disease. Lancet 1983; ii: 1457-59. 2. Barbeau A, Cloutier T, Roy M, Plasse L, Paris S, Poirier J. Ecogenetics of Parkinson’s disease: 4-hydroxylation of debrisoquine. Lancet 1985; ii: 1213-16. 3. Poirier J, Roy M, Campanella G, Cloutier T, Paris S. Debrisoquine metabolism in parkinsonian patients treated with antihistamine drugs. Lancet 1987; ii: 386. 4. Benitez J, Ladero JM, Jimenez FJ, et al. Oxidative polymorphism of debrisoquine in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1990; 53: 289-92. 5. Tanner CM, Chen B, Wang WZ, et al. Environmental factors in the etiology of Parkinson’s disease. Can J Neurol Sci 1987; 14 (suppl): 419-23. 6. Fonne-Pfister R, Bargetzi MJ, Meyer UA. MPTP, the neurotoxin inducing Parkinson’s disease is a potent competitive inhibitor of human
cytochrome P450 isozymes (P450 buf1, P450db1) catalyzing debrisoquine 4-hydroxylation. Biochem Biophys Res Commun 1987; and
rat
148: 1144-50. 7. Ohtas S, Tachikawa O, Makino Y, et al. Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer. Life Sci 1990; 46: 599-605. 8. Daly AK, Armstrong M, Monkman SC, et al. Genetic and metabolic criteria for the assignment of debrisoquine 4-hydroxylation (cytochrome P4502D6) phenotypes. Pharmacogenetics 1991; 1: 33-41. 9. Tyndale R, Aoyama T, Broly F, et al. Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype. Pharmacogenetics 1991; 1: 26-32.
10. Tyndalc RF, Sunahara R, Inaba T, P45011D1
et
al. Neuronal cytochrome
(debrisoquine/sparteine-type): potent inhibition of activity
by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. Mol Pharmacol
1991; 40: 63-68.
ADDRESSES. Pharmacogenetics Research Unit (M. Armstrong, BSc, A. K. Daly, PhD, S. Cholerton, PhD, Prof J. R Idle, PhD), and Wolfson Unit of Clinical Pharmacology (D N Bateman, FRCP), Department of Pharmacological Sciences, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Correspondence to Prof J R Idle.
Sensitivity of serological assays to identify blood donors with hepatitis C viraemia
Blood donors at high risk of hepatitis C virus (HCV) infection were tested for viraemia by the polymerase chain reaction (PCR). PCR results were accepted as positive only if reactive in 3 of 4 tests and if confirmed in an independent laboratory. The sera were also tested by 6 different assays to determine the ability of current serological assays to detect viraemic blood donors. Of 19 PCR-positive sera, only 13 (68%) were detected by the most sensitive of the serological assays. If these results are confirmed, automated PCR assays may be required for blooddonor screening to prevent transmission of HCV.
Anti-HCV-positive blood readily transmits HCV infection.1 But how sensitive are existing serological assays for the detection of anti-HCV antibodies and thereby the identification of infectious blood donors? Zanetti et aP describe 3 blood donors with viraemia detected by the polymerase chain reaction (PCR) who were seronegative by standard anti-HCV enzyme-linked immunosorbent assay (ELISA, Ortho). Aach et aP found that first-generation (anti-ClOO-3) ELISA assays detected 81%, and secondgeneration ELISA assays 93%, of donors implicated in the transmission of non-A, non-B hepatitis, but cases had to meet strict clinical criteria for the diagnosis of hepatitis. We have observed transfused patients with little or no increase in circulating transaminase concentrations who acquired chronic HCV viraemia detected by PCR, with or without accompanying anti-HCV seroconversion (unpublished observations). To investigate the sensitivity of anti-HCV serological assays we tested samples from blood donors at high risk of HCV infection by PCR, and then retested these samples by available immunoassays.
Disposable pipettes were used to sample plasma from 108 donors who had alanine aminotransferase concentrations above 100 IU/1. Samples were tested on 4 different occasions in our laboratory; nested PCR assays were done with primer pairs from the 5’ non-coding region as previously described4 and only samples positive in at least 3 of 4 tests were considered positive and then sent under code to the Liver Diseases Section, National Institutes of Health, where they were retested. Weakly positive samples were tested after cold precipitation with 10% polyethylene glycol. Blood from 25 of these 108 high-risk donors was found to be positive by PCR, 19 of which were independently confirmed to be positive at NIH. To provide an estimate of HCV-RNA titre, cDNA from positive samples was serially diluted in 0 01 mol/1 "tris", and
1019
SENSITIVITY OF SEROLOGICAL ASSAYS FOR DETECTION OF PCR-POSITIVE BLOOD DONORS
test-which in turn would need considerable progress towards a contamination-proof, automated, and practicable PCR assay technique. This research was supported in part by Pharmacia Genetic Engineering, the Liver Research Foundation of Japan, and the New York Blood Center. We thank Dr Syunji Mishiro, Institute of Immunology, Tokyo, for anti-GOR assay kits and Mrs M. Jaffrey for technical assistance
REFERENCES der Poel CL, Reesink HW, Schaasberg W, et al. Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 1990; 335: 558-60. 2. Zanetti AR, Tanzi E, Zehender G, et al. Hepatitis C virus RNA in symptomless donors implicated in post-transfusion non-A, non-B hepatitis. Lancet 1990; 336: 448. 3. Aach RD, Stevens CE, Hollinger FB, et al. Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and secondgeneration assays. N Engl J Med 1991; 325: 1325-29. 4. Inchauspé G, Abe K, Zebedee SL, Nasoff MS, Prince AM. Use of conserved sequences from hepatitis C virus for the detection of viral RNA in infected sera by PCR. Hepatology 1991; 14: 595-600. 5. Hosein B, Fang CT, Popovsky MA, Ye J, Zhang M, Wang CY. Improved serodiagnosis of hepatitis C virus infection with synthetic peptide antigen from capsid protein. Proc Natl Acad Sci USA 1991; 88: 3647-51. 6. Nasoff M, Zebedee SL, Inchauspé G, Prince AM. Identification of an immunodominant epitope within the capsid proteins of hepatitis C virus. Proc Natl Acad Sci USA 1991; 88: 5462-66. 7. Mishiro S, Hoshi Y, Takeda K, et al. Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process. Lancet 1990; 336: 1400-03. 8. Farci P, Alter HJ, Wong D, et al. A long-term study of hepatitis C virus replication in non-A, non-B Hepatitis. N Engl J Med 1991; 325: 98-104. 9. Simmonds P, Zhang LQ, Watson HG, et al. Hepatitis C quantification and sequencing in blood products, haemophiliacs, and drug users. Lancet 1990; 336: 1469-72. 1.
Results shown as number found
positive by that assay (% of those posltlve by PCR).
0001 moljl edetic acid buffer (pH 8) that contained 100 ltgJml salmon sperm DNA. This analysis is based on the 19 doubly confirmed samples, which were also tested by an anti-C100-3 second-generation ELISA (kindly provided by Dr 1. K. Mushahwar of Abbott Laboratories), recombinant immunoblot assay (RIBA II, Ortho), and an anti-HCV peptide-based assay (UBI),s in accordance with the manufacturers’ directions. Samples were also tested by ELISA for antibody to an HCV-capsid fusion protein (anti-CAP)6 and for anti-GOR.7
The most sensitive serological assays (second-generation anti-HCV ELISA [Abbott], anti-capsid ELISA, and anti-HCV EIA [UBI]) were positive for 13 (68%) of the 19 PCR-positive sera; all three assays were positive in 12 of these 13 sera (table). RIBA II was less sensitive, as was anti-GOR, an antibody directed to a host-encoded determinant which shows remarkable specificity for HCV infection.7 The sensitivity of the serological assays was directly related to the HCV-RNA titre of the specimen, and was much greater for specimens with high HCV-RNA content (table). The infectivity of specimens with low HCV-RNA content, which were poorly detected by the immunoassays, is not clear but transmission of infection has been observed in chimpanzees with an inoculum that had an HCV-DNA titre of 107 by PCR,8 Furthermore, specimens are likely to contain 4000 times the number of HCV-RNA molecules indicated by the dilution end-point titre per ml plasma, because only 50 III of serum was tested by PCR and the efficacy of cDNA synthesis is estimated to be 5%.9 6 specimens that, when undiluted, were PCR-positive in our laboratory were not found to be positive in the collaborating laboratory and are not included in the analysis. It is not known whether these reflect contamination or whether the PCR assays used at NIH were less sensitive. If these samples are truly PCR-positive, the sensitivity of the serological assays would be even lower (52%). On the other hand, the approach we used clearly relies absolutely upon the specificity of the PCR assays. Nevertheless, if the results are confirmed, at least 30% of high-risk donors with HCV viraemia who have raised alanine aminotransferase concentrations are seronegative for anti-HCV antibodies by available screening assays. Immunodominant epitopes of HCV have been well studied, and it seems unlikely that future immunoassays will show greatly improved sensitivity. There also seems little reason to suppose that the relative sensitivity of serological screening would improve among donors at lower risk of HCV infection. Indeed, there appears to be a risk that some HCV-infected subjects, especially those with limited viral replication, are unable to mount a detectable antibody response yet their blood may contain sufficient viral particles to transmit HCV and lead to chronic infection, with or without clinically apparent hepatitis, in transfusion recipients. To identify such donors so that their blood is not transfused may require the use of PCR as a routine screening
van
ADDRESSES: First Department of Pathology, Nihon University School of Medicine, Tokyo 173, Japan (M Sugitani, MD); Laboratory of Virology and Parasitology, New York Blood Center, 310 East 67th Street, New York, NY 10021 (G Inchauspé, PhD, A M Prince, MD); and Liver Disease Section, National Institutes of Health, Bethesda, Maryland 20892, USA (M. Shindo, MD). Correspondence to Dr Alfred Prince.
Variation in the quality of cardiopulmonary resuscitation
During instruction in basic cardiopulmonary resuscitation (CPR) skills, cardiac massage and mouth-to-mouth ventilation are applied without interruption for no longer than a few minutes. The aim of this study was to see if the quality of technique during the first 2 min of CPR reflects the resuscitators ability to perform CPR over a 15 min period. done with a resuscitation which recordings of several variables were made at 2, 5, 10, and 15 min after the start of CPR. 60 lay volunteers who had received CPR training were studied, and six variables that describe the quality of CPR technique were recorded and scored with a predefined scoring system. No deterioration in CPR skills was seen during 15 min. We conclude that the initial 2 min assessment reflects the resuscitators ability to perform CPR over a longer
Assessments
were
mannequin from
period.
Lancet 1992; 339: 1019-20.
chromosomes in controls to 1 of 106 (0-9%) in cases (r’=119, p < 0-001). The excess of CYP2D6B alleles among patients with Parkinson’s disease was almost entirely accounted for by a doubled frequency of the wt/CYP2D6B genotype compared with controls (37-7% 18-1%). The numbers studied were too small to detect any changes in homozygous PM frequency (2 in both groups), and we did not attempt to identify the rare CYP2D6C allele, also associated with deficient CYP2D6-mediated metabolism.9 How might the hepatic CYP2D6 isozyme influence the onset of Parkinson’s disease? Apart from a possible role in environmental neurotoxin inactivation, recent evidence indicates that the gene product may influence brain function. A partial cDNA with 100% sequence homology to CYP2D6 has recently been cloned from the caudate nucleus in man, to and CYP2D6-like metabolic activity is distributed throughout the canine brain; this protein has an affinity for drugs that interact with the neuronal dopamine transporter. to Individuals homozygous or heterozygous for CYP2D6 mutations may therefore have lower rates of CYP2D6-mediated chemical metabolism in the brain and altered dopamine homoeostasis. In this preliminary study we found that the commonest genotype to confer impaired debrisoquine metabolism, wt/CYP2D6B, is twice as common among patients with Parkinson’s disease than in the normal population. These findings would not be influenced by concomitant drug therapy. However, we did not observe any overall increase in the total number of mutant alleles among parkinsonian patients and it is possible that a specific genetic mechanism, such as linkage disequilibrium, underlies the apparent association between Parkinson’s disease and the CYP2D6B allele, or indeed that the findings of this small pilot study, with controls matched for ethnicity alone, could be explained by chance. Larger controlled studies, perhaps with an emphasis on patients with early onset of Parkinson’s
disease, are now required. We thank Dr R. G. Cooper and Dr D. Bates for assistance in recruitment and Dr N. Caporaso for statistical advice. Supported Wellcome Trust, BAT Ltd, and Bayer UK plc.
patient by the
REFERENCES 1. Calne DB, Langston JW. Aetiology of Parkinson’s disease. Lancet 1983; ii: 1457-59. 2. Barbeau A, Cloutier T, Roy M, Plasse L, Paris S, Poirier J. Ecogenetics of Parkinson’s disease: 4-hydroxylation of debrisoquine. Lancet 1985; ii: 1213-16. 3. Poirier J, Roy M, Campanella G, Cloutier T, Paris S. Debrisoquine metabolism in parkinsonian patients treated with antihistamine drugs. Lancet 1987; ii: 386. 4. Benitez J, Ladero JM, Jimenez FJ, et al. Oxidative polymorphism of debrisoquine in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1990; 53: 289-92. 5. Tanner CM, Chen B, Wang WZ, et al. Environmental factors in the etiology of Parkinson’s disease. Can J Neurol Sci 1987; 14 (suppl): 419-23. 6. Fonne-Pfister R, Bargetzi MJ, Meyer UA. MPTP, the neurotoxin inducing Parkinson’s disease is a potent competitive inhibitor of human
cytochrome P450 isozymes (P450 buf1, P450db1) catalyzing debrisoquine 4-hydroxylation. Biochem Biophys Res Commun 1987; and
rat
148: 1144-50. 7. Ohtas S, Tachikawa O, Makino Y, et al. Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer. Life Sci 1990; 46: 599-605. 8. Daly AK, Armstrong M, Monkman SC, et al. Genetic and metabolic criteria for the assignment of debrisoquine 4-hydroxylation (cytochrome P4502D6) phenotypes. Pharmacogenetics 1991; 1: 33-41. 9. Tyndale R, Aoyama T, Broly F, et al. Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype. Pharmacogenetics 1991; 1: 26-32.
10. Tyndalc RF, Sunahara R, Inaba T, P45011D1
et
al. Neuronal cytochrome
(debrisoquine/sparteine-type): potent inhibition of activity
by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. Mol Pharmacol
1991; 40: 63-68.
ADDRESSES. Pharmacogenetics Research Unit (M. Armstrong, BSc, A. K. Daly, PhD, S. Cholerton, PhD, Prof J. R Idle, PhD), and Wolfson Unit of Clinical Pharmacology (D N Bateman, FRCP), Department of Pharmacological Sciences, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Correspondence to Prof J R Idle.
Sensitivity of serological assays to identify blood donors with hepatitis C viraemia
Blood donors at high risk of hepatitis C virus (HCV) infection were tested for viraemia by the polymerase chain reaction (PCR). PCR results were accepted as positive only if reactive in 3 of 4 tests and if confirmed in an independent laboratory. The sera were also tested by 6 different assays to determine the ability of current serological assays to detect viraemic blood donors. Of 19 PCR-positive sera, only 13 (68%) were detected by the most sensitive of the serological assays. If these results are confirmed, automated PCR assays may be required for blooddonor screening to prevent transmission of HCV.
Anti-HCV-positive blood readily transmits HCV infection.1 But how sensitive are existing serological assays for the detection of anti-HCV antibodies and thereby the identification of infectious blood donors? Zanetti et aP describe 3 blood donors with viraemia detected by the polymerase chain reaction (PCR) who were seronegative by standard anti-HCV enzyme-linked immunosorbent assay (ELISA, Ortho). Aach et aP found that first-generation (anti-ClOO-3) ELISA assays detected 81%, and secondgeneration ELISA assays 93%, of donors implicated in the transmission of non-A, non-B hepatitis, but cases had to meet strict clinical criteria for the diagnosis of hepatitis. We have observed transfused patients with little or no increase in circulating transaminase concentrations who acquired chronic HCV viraemia detected by PCR, with or without accompanying anti-HCV seroconversion (unpublished observations). To investigate the sensitivity of anti-HCV serological assays we tested samples from blood donors at high risk of HCV infection by PCR, and then retested these samples by available immunoassays.
Disposable pipettes were used to sample plasma from 108 donors who had alanine aminotransferase concentrations above 100 IU/1. Samples were tested on 4 different occasions in our laboratory; nested PCR assays were done with primer pairs from the 5’ non-coding region as previously described4 and only samples positive in at least 3 of 4 tests were considered positive and then sent under code to the Liver Diseases Section, National Institutes of Health, where they were retested. Weakly positive samples were tested after cold precipitation with 10% polyethylene glycol. Blood from 25 of these 108 high-risk donors was found to be positive by PCR, 19 of which were independently confirmed to be positive at NIH. To provide an estimate of HCV-RNA titre, cDNA from positive samples was serially diluted in 0 01 mol/1 "tris", and
1019
SENSITIVITY OF SEROLOGICAL ASSAYS FOR DETECTION OF PCR-POSITIVE BLOOD DONORS
test-which in turn would need considerable progress towards a contamination-proof, automated, and practicable PCR assay technique. This research was supported in part by Pharmacia Genetic Engineering, the Liver Research Foundation of Japan, and the New York Blood Center. We thank Dr Syunji Mishiro, Institute of Immunology, Tokyo, for anti-GOR assay kits and Mrs M. Jaffrey for technical assistance
REFERENCES der Poel CL, Reesink HW, Schaasberg W, et al. Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 1990; 335: 558-60. 2. Zanetti AR, Tanzi E, Zehender G, et al. Hepatitis C virus RNA in symptomless donors implicated in post-transfusion non-A, non-B hepatitis. Lancet 1990; 336: 448. 3. Aach RD, Stevens CE, Hollinger FB, et al. Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and secondgeneration assays. N Engl J Med 1991; 325: 1325-29. 4. Inchauspé G, Abe K, Zebedee SL, Nasoff MS, Prince AM. Use of conserved sequences from hepatitis C virus for the detection of viral RNA in infected sera by PCR. Hepatology 1991; 14: 595-600. 5. Hosein B, Fang CT, Popovsky MA, Ye J, Zhang M, Wang CY. Improved serodiagnosis of hepatitis C virus infection with synthetic peptide antigen from capsid protein. Proc Natl Acad Sci USA 1991; 88: 3647-51. 6. Nasoff M, Zebedee SL, Inchauspé G, Prince AM. Identification of an immunodominant epitope within the capsid proteins of hepatitis C virus. Proc Natl Acad Sci USA 1991; 88: 5462-66. 7. Mishiro S, Hoshi Y, Takeda K, et al. Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process. Lancet 1990; 336: 1400-03. 8. Farci P, Alter HJ, Wong D, et al. A long-term study of hepatitis C virus replication in non-A, non-B Hepatitis. N Engl J Med 1991; 325: 98-104. 9. Simmonds P, Zhang LQ, Watson HG, et al. Hepatitis C quantification and sequencing in blood products, haemophiliacs, and drug users. Lancet 1990; 336: 1469-72. 1.
Results shown as number found
positive by that assay (% of those posltlve by PCR).
0001 moljl edetic acid buffer (pH 8) that contained 100 ltgJml salmon sperm DNA. This analysis is based on the 19 doubly confirmed samples, which were also tested by an anti-C100-3 second-generation ELISA (kindly provided by Dr 1. K. Mushahwar of Abbott Laboratories), recombinant immunoblot assay (RIBA II, Ortho), and an anti-HCV peptide-based assay (UBI),s in accordance with the manufacturers’ directions. Samples were also tested by ELISA for antibody to an HCV-capsid fusion protein (anti-CAP)6 and for anti-GOR.7
The most sensitive serological assays (second-generation anti-HCV ELISA [Abbott], anti-capsid ELISA, and anti-HCV EIA [UBI]) were positive for 13 (68%) of the 19 PCR-positive sera; all three assays were positive in 12 of these 13 sera (table). RIBA II was less sensitive, as was anti-GOR, an antibody directed to a host-encoded determinant which shows remarkable specificity for HCV infection.7 The sensitivity of the serological assays was directly related to the HCV-RNA titre of the specimen, and was much greater for specimens with high HCV-RNA content (table). The infectivity of specimens with low HCV-RNA content, which were poorly detected by the immunoassays, is not clear but transmission of infection has been observed in chimpanzees with an inoculum that had an HCV-DNA titre of 107 by PCR,8 Furthermore, specimens are likely to contain 4000 times the number of HCV-RNA molecules indicated by the dilution end-point titre per ml plasma, because only 50 III of serum was tested by PCR and the efficacy of cDNA synthesis is estimated to be 5%.9 6 specimens that, when undiluted, were PCR-positive in our laboratory were not found to be positive in the collaborating laboratory and are not included in the analysis. It is not known whether these reflect contamination or whether the PCR assays used at NIH were less sensitive. If these samples are truly PCR-positive, the sensitivity of the serological assays would be even lower (52%). On the other hand, the approach we used clearly relies absolutely upon the specificity of the PCR assays. Nevertheless, if the results are confirmed, at least 30% of high-risk donors with HCV viraemia who have raised alanine aminotransferase concentrations are seronegative for anti-HCV antibodies by available screening assays. Immunodominant epitopes of HCV have been well studied, and it seems unlikely that future immunoassays will show greatly improved sensitivity. There also seems little reason to suppose that the relative sensitivity of serological screening would improve among donors at lower risk of HCV infection. Indeed, there appears to be a risk that some HCV-infected subjects, especially those with limited viral replication, are unable to mount a detectable antibody response yet their blood may contain sufficient viral particles to transmit HCV and lead to chronic infection, with or without clinically apparent hepatitis, in transfusion recipients. To identify such donors so that their blood is not transfused may require the use of PCR as a routine screening
van
ADDRESSES: First Department of Pathology, Nihon University School of Medicine, Tokyo 173, Japan (M Sugitani, MD); Laboratory of Virology and Parasitology, New York Blood Center, 310 East 67th Street, New York, NY 10021 (G Inchauspé, PhD, A M Prince, MD); and Liver Disease Section, National Institutes of Health, Bethesda, Maryland 20892, USA (M. Shindo, MD). Correspondence to Dr Alfred Prince.
Variation in the quality of cardiopulmonary resuscitation
During instruction in basic cardiopulmonary resuscitation (CPR) skills, cardiac massage and mouth-to-mouth ventilation are applied without interruption for no longer than a few minutes. The aim of this study was to see if the quality of technique during the first 2 min of CPR reflects the resuscitators ability to perform CPR over a 15 min period. done with a resuscitation which recordings of several variables were made at 2, 5, 10, and 15 min after the start of CPR. 60 lay volunteers who had received CPR training were studied, and six variables that describe the quality of CPR technique were recorded and scored with a predefined scoring system. No deterioration in CPR skills was seen during 15 min. We conclude that the initial 2 min assessment reflects the resuscitators ability to perform CPR over a longer
Assessments
were
mannequin from
period.
Lancet 1992; 339: 1019-20.