1377
paper showing that audit is unlikely to substantially reduce the number ofintrapartum operations. What we need is a more specific method of monitoring, possibly based on non-invasive
multichannel monitoring.
already reported.3 In 60 patients with primary antibody deficiencies who received replacement therapy with 200-400 mg/kg IVIG every 2-3 weeks
as
for
Department of Obstetrics and Gynaecology, University of Leeds, St James’s University Hospital,
median of 5 years, 3 had clinical and serological evidence of hepatitis. Chronic hepatitis later developed in 2 patients. The 3 patients with acute and chronic hepatitis received different lots of a preparation with high titres of anti-HCV antibodies. We suspected, but we could not prove, that hepatitis was caused by the NANBH virus, because we found no serological evidence of hepatitis B antigen and the patients had no known risk factors for hepatitis B. We have found that when anti-HCV-positive serum is diluted in anti-HCV-negative IVIG an antibody-positive reaction is found at high dilution (1:1024). Thus, even a low number of anti-HCVpositive plasma units could be responsible for the positivity of a lot of IVIG prepared from a pool of thousands of donors. Our data support the view that anti-HCV positivity of blood products varies depending on country of origin of plasma donation. a
acute
R. J. LILFORD
Leeds LS9 7TF, UK
Erythema nodosum and hepatitis C SIR,-Dr Reichel and Dr Mauro (Sept 29, p 822) described acute urticaria associated with acute hepatitis C virus (HCV) infection. We report a patient with acute hepatitis caused by HCV who presented with thrombocytopenia and erythema nodosum. A 26-year-old man with eczematous dermatitis had generalised arthromyalgias for 10 days, followed by sudden onset of bilateral tender nodules on the anterior aspect of the legs together with petechiae and fever. He had had a dental procedure 6 weeks earlier and had not been taking any drug. Liver enzymes were raised and white-cell count was 3410/tl with 3% bands, 26-6% neutrophils, 578% lymphocytes, and 10% monocytes. Platelet count was 25 000/1 and haemogloblin was 10-3 g/dl. Tests for hepatitis B surface antigen, and IgM antibodies to hepatitis A and B, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus antibodies and antigen were not found. Platelet autoantibodies were negative, while a direct Coombs’ test was positive. Bone marrow was hypoplastic, with an increased iron content and increased numbers of plasma cells. An HCV antibody The patient received only symptomatic treatment. 4 weeks later liver enzymes were normal, nodules were slowly resolving, and haematological counts were within the normal range. This patient had dermatological findings and haematological abnormalities associated with seroconversion to HCV. Acute hepatitis is sometimes associated with acute thrombocytopenia and test was positive.
with dermatological fmdingsY We conclude that acute HCV infection may cause acute thrombocytopenia and erythema nodosum. PERE DOMINGO JOSEP RIS ESTEBAN MARTINEZ FREDERIC CASAS
Department of Internal Medicine, Hospital de la Santa Creu Sant Pau, 08025 Barcelona, Spain
McIntyre N. Clinical presentation of acute viral hepatitis. Br Med Bull 1990; 46: 533-47. 2. Young NS. Flaviviruses and bone marrow failure. JAMA 1990; 264: 3065-68. 1.
Hepatitis C virus antibodies in gammaglobulin in non-A, and blood donors is well established.l NANBH has also been reported in patients with X-linked agammaglobulinaemia or common variable with after treatment intravenous immunodeficiency immunoglobulin (IVIG)Z We have tested 50 lots of IVIG from 11 brands for anti-HCV antibodies by ELISA (Ortho). HCV antibodies were found in 26 (52%) lots. According to the brand and the country of origin of the donor plasma anti-HCV antibody was found in 0 to 100% of lots. The number of antibody-positive lots and total lots tested are shown by country of manufacture for IVIG made both before and after 1987, the year in which testing for anti-HIV antibodies in each plasma unit began:
S!R,—The involvement of hepatitis C virus (HCV) hepatitis (NANBH) in transfusion recipients
non-B
Preparation Italy (3 brands) France (1 brand) Switzerland (2 brands) Austria (I brand) Germany (2 brands) USA (2 brands)
donations are common in American, German, and Austrian pools,
Pre-1987 Post-1987
0/3 0/2 0/7 13/14 5/5 1/1
0/4 1/2 1/6 3/3 0/1 2/2 The percentage of positive lots fell from 59% pre-1987 post-1987. Our results imply that
to
39%
anti-HCV-positive plasma
Department of Allergy and Clinical Immunology, University of Rome "La Sapienza", 00185 Rome, Italy
ISABELLA QUINTI ROBERTO PAGANELLI ENRICO SCALA EMMA GUERRA IVANO MEZZAROMA GIAN PIERO D’OFFIZI FERNANDO AIUTI
1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989; 244: 359-62. 2. Lever AML, Webster ADB, Brown D, Thomas HC. Non A, non B hepatitis occurring m agammaglobulinaemic patients after intravenous immunoglobulin. Lancet 1984; ii: 1062-64. 3. Minor P, Pipkin P, Thorpe R, Thomas D. Antibody to hepatitis C virus in plasma pools. Lancet 1990; 336: 188.
Brachioradial
delay
SIR,-Dr Leach and Dr McBrien (May 19, p 1199) describe delay of the pulse between brachial and radial arteries as a new clinical indicator of severity of aortic stenosis. They propose that this could be an important sign in the clinical evaluation of patients with heart murmur.
We have not been able to confirm the findings of Leach and McBrien. In studies of the arterial pulse, recorded invasively and non-invasively,l-4 we have not found any unusual delay of the pulse between central and peripheral arteries in patients with aortic stenosis, nor any unusual delay between the brachial and radial arteries. Indeed, in our article,2 cited by Leach and McBrien, there was reduced delay between the peak of the pulse in central and peripheral arteries in aortic stenosis compared with mitral stenosis, despite similar delays in the foot of the wave. Findings were attributed to relatively long duration of systole in patients with aortic stenosis, with resultant summation of incident and reflected waves.
Leach and McBrien’s findings might be attributable to the highly unusual waveforms they recorded. These are quite unlike pressure waves recorded directly with an intra-arterial catheter, or indirectly with a tonometer or sphygmograph.l-4 These waves indicate that pressure is lower in the midpart of the pulse than at the end of diastole. There is no suggestion of the typical anacrotic contour in the patient with aortic stenosis. Leach and McBrien measured delay from the pulse peak, whereas delay for determination of pulse wave velocity should be recorded from the foot of the pulse to eliminate the effects of wave reflection.1,3 Their value of 53-5 m/s (SE 2-6) for brachioradial delay suggests that pulse-wave velocity in the upper limb of patients with aortic stenosis was around 4-7 m/s (assuming 25 cm between recording sites). This value is far lower than any determination for man-even for children.1 Since wave velocity is an acknowledged measure of arterial stiffness, Leach and McBrien’s findings suggest that upper-limb arteries of patients with aortic stenosis are far more compliant than those of children; there is no other evidence that this is the case. In nine patients with aortic stenosis reviewed by us recently, upper-limb pulse-wave velocity
paper showing that audit is unlikely to substantially reduce the number ofintrapartum operations. What we need is a more specific method of monitoring, possibly based on non-invasive
multichannel monitoring.
already reported.3 In 60 patients with primary antibody deficiencies who received replacement therapy with 200-400 mg/kg IVIG every 2-3 weeks
as
for
Department of Obstetrics and Gynaecology, University of Leeds, St James’s University Hospital,
median of 5 years, 3 had clinical and serological evidence of hepatitis. Chronic hepatitis later developed in 2 patients. The 3 patients with acute and chronic hepatitis received different lots of a preparation with high titres of anti-HCV antibodies. We suspected, but we could not prove, that hepatitis was caused by the NANBH virus, because we found no serological evidence of hepatitis B antigen and the patients had no known risk factors for hepatitis B. We have found that when anti-HCV-positive serum is diluted in anti-HCV-negative IVIG an antibody-positive reaction is found at high dilution (1:1024). Thus, even a low number of anti-HCVpositive plasma units could be responsible for the positivity of a lot of IVIG prepared from a pool of thousands of donors. Our data support the view that anti-HCV positivity of blood products varies depending on country of origin of plasma donation. a
acute
R. J. LILFORD
Leeds LS9 7TF, UK
Erythema nodosum and hepatitis C SIR,-Dr Reichel and Dr Mauro (Sept 29, p 822) described acute urticaria associated with acute hepatitis C virus (HCV) infection. We report a patient with acute hepatitis caused by HCV who presented with thrombocytopenia and erythema nodosum. A 26-year-old man with eczematous dermatitis had generalised arthromyalgias for 10 days, followed by sudden onset of bilateral tender nodules on the anterior aspect of the legs together with petechiae and fever. He had had a dental procedure 6 weeks earlier and had not been taking any drug. Liver enzymes were raised and white-cell count was 3410/tl with 3% bands, 26-6% neutrophils, 578% lymphocytes, and 10% monocytes. Platelet count was 25 000/1 and haemogloblin was 10-3 g/dl. Tests for hepatitis B surface antigen, and IgM antibodies to hepatitis A and B, cytomegalovirus, and Epstein-Barr virus were negative. Human immunodeficiency virus antibodies and antigen were not found. Platelet autoantibodies were negative, while a direct Coombs’ test was positive. Bone marrow was hypoplastic, with an increased iron content and increased numbers of plasma cells. An HCV antibody The patient received only symptomatic treatment. 4 weeks later liver enzymes were normal, nodules were slowly resolving, and haematological counts were within the normal range. This patient had dermatological findings and haematological abnormalities associated with seroconversion to HCV. Acute hepatitis is sometimes associated with acute thrombocytopenia and test was positive.
with dermatological fmdingsY We conclude that acute HCV infection may cause acute thrombocytopenia and erythema nodosum. PERE DOMINGO JOSEP RIS ESTEBAN MARTINEZ FREDERIC CASAS
Department of Internal Medicine, Hospital de la Santa Creu Sant Pau, 08025 Barcelona, Spain
McIntyre N. Clinical presentation of acute viral hepatitis. Br Med Bull 1990; 46: 533-47. 2. Young NS. Flaviviruses and bone marrow failure. JAMA 1990; 264: 3065-68. 1.
Hepatitis C virus antibodies in gammaglobulin in non-A, and blood donors is well established.l NANBH has also been reported in patients with X-linked agammaglobulinaemia or common variable with after treatment intravenous immunodeficiency immunoglobulin (IVIG)Z We have tested 50 lots of IVIG from 11 brands for anti-HCV antibodies by ELISA (Ortho). HCV antibodies were found in 26 (52%) lots. According to the brand and the country of origin of the donor plasma anti-HCV antibody was found in 0 to 100% of lots. The number of antibody-positive lots and total lots tested are shown by country of manufacture for IVIG made both before and after 1987, the year in which testing for anti-HIV antibodies in each plasma unit began:
S!R,—The involvement of hepatitis C virus (HCV) hepatitis (NANBH) in transfusion recipients
non-B
Preparation Italy (3 brands) France (1 brand) Switzerland (2 brands) Austria (I brand) Germany (2 brands) USA (2 brands)
donations are common in American, German, and Austrian pools,
Pre-1987 Post-1987
0/3 0/2 0/7 13/14 5/5 1/1
0/4 1/2 1/6 3/3 0/1 2/2 The percentage of positive lots fell from 59% pre-1987 post-1987. Our results imply that
to
39%
anti-HCV-positive plasma
Department of Allergy and Clinical Immunology, University of Rome "La Sapienza", 00185 Rome, Italy
ISABELLA QUINTI ROBERTO PAGANELLI ENRICO SCALA EMMA GUERRA IVANO MEZZAROMA GIAN PIERO D’OFFIZI FERNANDO AIUTI
1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989; 244: 359-62. 2. Lever AML, Webster ADB, Brown D, Thomas HC. Non A, non B hepatitis occurring m agammaglobulinaemic patients after intravenous immunoglobulin. Lancet 1984; ii: 1062-64. 3. Minor P, Pipkin P, Thorpe R, Thomas D. Antibody to hepatitis C virus in plasma pools. Lancet 1990; 336: 188.
Brachioradial
delay
SIR,-Dr Leach and Dr McBrien (May 19, p 1199) describe delay of the pulse between brachial and radial arteries as a new clinical indicator of severity of aortic stenosis. They propose that this could be an important sign in the clinical evaluation of patients with heart murmur.
We have not been able to confirm the findings of Leach and McBrien. In studies of the arterial pulse, recorded invasively and non-invasively,l-4 we have not found any unusual delay of the pulse between central and peripheral arteries in patients with aortic stenosis, nor any unusual delay between the brachial and radial arteries. Indeed, in our article,2 cited by Leach and McBrien, there was reduced delay between the peak of the pulse in central and peripheral arteries in aortic stenosis compared with mitral stenosis, despite similar delays in the foot of the wave. Findings were attributed to relatively long duration of systole in patients with aortic stenosis, with resultant summation of incident and reflected waves.
Leach and McBrien’s findings might be attributable to the highly unusual waveforms they recorded. These are quite unlike pressure waves recorded directly with an intra-arterial catheter, or indirectly with a tonometer or sphygmograph.l-4 These waves indicate that pressure is lower in the midpart of the pulse than at the end of diastole. There is no suggestion of the typical anacrotic contour in the patient with aortic stenosis. Leach and McBrien measured delay from the pulse peak, whereas delay for determination of pulse wave velocity should be recorded from the foot of the pulse to eliminate the effects of wave reflection.1,3 Their value of 53-5 m/s (SE 2-6) for brachioradial delay suggests that pulse-wave velocity in the upper limb of patients with aortic stenosis was around 4-7 m/s (assuming 25 cm between recording sites). This value is far lower than any determination for man-even for children.1 Since wave velocity is an acknowledged measure of arterial stiffness, Leach and McBrien’s findings suggest that upper-limb arteries of patients with aortic stenosis are far more compliant than those of children; there is no other evidence that this is the case. In nine patients with aortic stenosis reviewed by us recently, upper-limb pulse-wave velocity
