Brachioradial delay

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 test was positive. 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 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 1378 9.1 m/s (SE 0-7) before surgery, and 9-5 m/s (SE 0-3) postoperatively. Any new clinical indicator of disease is potentially useful. Before the findings of Leach and McBrien are applied more widely, our points need to be addressed. was Medical Professorial Unit, University of New South Wales, St Vincent’s Hospital, Darlinghurst, NSW 2010, Australia MICHAEL F. O’ROURKE ALBERT P. AVOLIO MOUSTAFA KARAMANOGLU DAVID GALLAGHER CHRISTOPHER SCHYVENS 1. Nichols WW, O’Rourke MF. McDonald’s blood flow in arteries, 3rd ed. London: Edward Arnold, 1990. 2. O’Rourke MF. Influence of ventricular ejection on the relationship between central aortic and brachial pressure pulse in man. Cardiovasc Res 1970; 4: 291-300. 3. O’Rourke MF. Arterial function in health and disease. Edinburgh: Churchill Livingstone, 1982. 4. Kelly R, Hayward C, Avolio A, O’Rourke M. Noninvasive determination of age-related changes in the human arterial pulse. Circulation 1989; 80: 1652-59. Heart attacks and sleep apnoea SiR,—The article by Dr Hung and colleagues (Aug 4, p 261) linking myocardial infarction (MI) with previously undiagnosed sleep apnoea is potentially important. However, before a cause-and-effect link is assumed the potential for error must be examined. The MI group included patients with mild and moderate heart failure in whom periodic respiration with apnoeas, hypopnoeas, and desaturation are common.’ MI patients with chronic lung disease whose oxygen saturations were 90% or above were also included; in such patients abnormal oxygenation during sleep can be expected.2,3 Were any of the patients taking anxiolytic, antihypertensive, diuretic, or beta-blocking drugs, which can interfere with nocturnal breathing? Controls were excluded only if they had evidence of ischaemic heart disease. They were significantly thinner (25 4 [SE 04] vs 27-3 [0.4] kg/m2) than the MI patients and were less likely to be smokers (13 vs 43%). Nor was any attempt made to match for other disorders such as chronic lung disease or hypertension. The lower percentage of smokers in the control group and the differing sleep oxygen saturations suggest that the awake oxygenation in the two groups was different. This would lead to the MI group having more "hypopnoeas" due to their lower position on the oxygen dissociation curve; the definition of hypopnoea used in this study required 4% desaturation. Neither quality nor duration of sleep were reported though respiratory events were given as per hour of "sleep". Our experience of studying healthy individuals for only one night in a sleep laboratory is that they sleep badly; this leads to a serious underestimation of the frequency of apnoea/hypopnoea per hour of sleep if sleep is not timed by electroencephalographic criteria. The MI group, conversely, had recent experience of sleeping in hospitals (5% were still inpatients and the mean post-myocardial infarction duration was 24 days) and may have slept much better. The apnoea frequency of the MI group was 6-9 (SE 1-2) h, which is not especially high for men of average age 55 and average body mass index 27-3 kg/m2. Current guidelines for the upper limit of normal apnoea-plus-hypopnoea frequency are around 15/h, and these were derived in patients of normal body weight.’4 We are unclear how the groupings of apnoea indices used in the multiple logistic regression were selected. The text suggests quartiles yet the apnoea index of the highest level was 5’3/h, which is lower than the mean (6-9/h). Was this choice made post hoc? Table III, giving the results and 95% confidence intervals of the multiple logistic regression analysis, contains an error in the second bottom line. Obstructive sleep apnoea is often due to obesity, especially to neck obesity.’ Since upper body obesity is also a better marker of coronary artery disease than overall obesityb this should have been allowed for, with hypertension and smoking. Mild obstructive sleep apnoea may thus be acting mainly as a marker of the more important risk factor, upper body obesity. The same arguments have recently been used to question whether sleep apnoea and snoring cause "essential" hypertension.’ The implications of Hung and colleagues’ paper are so enormous--suggesting a sleep study on every middle-aged manthat we must be sure of the facts, and this study is not entirely convincing. Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK J. R. STRADLING Department of Respiratory Medicine, University of Edinburgh, City Hospital, Edinburgh N. J. DOUGLAS 1. Dark DS, Pingleton SK, Kerby GR, et al. Breathing pattern abnormalities and arterial desaturation during sleep m the congestive heart failure syndrome. Chest 1987; 91: 833-36. 2. Connaughton JJ, Catterall JR, Elton RA, Stradling JR, Douglas NJ Do sleep studies contribute to management of patients with severe chronic obstructive pulmonary disease? Am Rev Respir Dis 1988; 138: 341-44. 3. Stradling JR, Lane DJ. Nocturnal hypoxaemia m chronic obstructive pulmonary disease. Clin Sci 1983; 64: 213-22. 4. Catterall JR, Calverley PMA, Shapiro CM, Flenley DC, Douglas NJ. Breathing and oxygenation during sleep are similar in normal men and normal women. Am Rev Respir Dis 1985; 132: 86-88. 5. Davies RJO, Stradling JR. The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apnoea syndrome. Eur Respir J 1990; 3: 509-14. 6. Larsson B, Svardsudd K, Welin L, et al. Abdominal adipose distribution, obesity and nsk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J 1984; 288: 1401-04. 7. Stradling JR. Sleep apnoea and hypertension. Thorax 1989; 44: 984-89. ** This letter has been shown to Dr Hung and colleagues, whose reply follows.-ED. L. SiR,—Though we intentionally excluded patients with severe heart failure and chronic lung disease, Dr Stradling and Dr Douglas feel that these two disorders could have increased the prevalence of sleep apnoea among our myocardial infarction (MI) patients. Interestingly, they later state that apnoea frequency among our MI patients was "not particularly high" when compared with a normal population. The studies of Dark et al,l to which Stradling and Douglas refer, and of Hanley et al,2 demonstrate that apnoeas associated with heart failure are overwhelmingly ( > 95%) central, both before and after treatment. In contrast, apnoeas in our MI patients were predominantly obstructive, as they were in controls (87% and 81 %, respectively). Average arterial oxygen saturations in the MI patients and controls were 93-65% and 942%, respectively (table n). We do not believe that the small difference in mean oxygen saturation would significantly increase the incidence of hypopnoeas in MI patients. Nevertheless, apnoeas, which are defined by absence of airflow and not by oxygen desaturation, were independently predictive of myocardial infarction. Hypopnoeas did not add to the predictive value of apnoeas. The major difference in drug therapy between the MI and control groups was use of beta-blockers by MI patients. However, an apnoea index in the upper quartile (> 5-3 h) was not significantly more frequent in MI patients who took beta-blockers compared with those who did not (ie, 39% [28/72] and 28% [8/29], respectively). As stated in our paper, only 5 MI patients took sedatives. We are unaware of any specific influence of antihypertensives and diuretics on nocturnal breathing. The control group without ischaemic heart disease were expected to have less obesity, hypertension, and smokers than the MI group. As the text makes clear, statistical methods controlled for these differences. While sleep was not staged, sleep time was estimated by a technician who was continually in attendance. Mean sleep time was only slightly less in the control than the MI group-62 h (SE = 0,12) vs 6-5 h (0-09), p=004. The estimated percentage of monitoring time spent asleep was not significantly different between the control and MI groups (88 vs 90%), and suggests that the quality of sleep was similar. The definition of an "upper limit of normal" for the apnoea or apnoea/hypopnoea index is arbitrary.3 We did not group cases by a preconceived definition of a "normal" and "abnormal" apnoea index but grouped all cases (n = 154) by quartiles of distribution of their apnoea index. From multiple logistic regression analysis we