428 CŒLIAC SYNDROME AND POLYMYOSITIS
SIR,-Inflammatory lesions which begin subacutely are notoriously hard to diagnose. The case reported in detail by Dr Henriksson and his colleagues (Aug. 7, p. 317) was, for example, diagnosed only after four years had elapsed. Presumably by then, the biochemical and histological changes had altered considerably. An earlier pathological process therefore probably induced the enteropathy and polymyositis in their four patients. Sarcoidosis is occasionally associated with the coeliac the syndrome,! peripheral neuropathy,2 polymyositis,3 seven of autoimmune disorders listed by Scott and Losowski,4 s and parathyroid dysfunction.6 Sarcoid infiltration greatly raises the level of humoral and cellular immunity and it generates immune complexes.’ Systemic spread of the sarcoid agent may produce granulomas in any organ, and the local immune response partly decides which syndrome arises. Sarcoidosis possibly caused the muscle disease and enteropathy in these four cases.
St. Luke’s Hospital, Guildford, Surrey GU1
3NT
GERALD A. MACGREGOR
standard in the presence of normal serum. This modification also eliminates another possible error (i.e., adsorption of I.F. to the test tubel1). Our modified method has been in routine use for four years, Of 1000 consecutive samples tested during the past 17 months 55 were positive for I.F. Ab. 7 of these were retested due to the presence of free vitamin B12. After adsorption with haemoglobin-coated charcoal 5 were still positive, whereas 2 could be
excluded as false positives. Another advantage of the modified method is the increased sensitivity. A blocking activity of 1.5 ng/ml can be reliably measured. With the original coated-charcoal method" we used a cut-off level of 2 ng/ml, but in practice we did not detect levels below 3 ng/ml due to the artifact caused by the binding capacity of the sample. 5 of the 53 true-positive patients in our series would not have been detected by the earlier used method.9 The additional effort needed for the modified method (four tubes per assay instead of two) seems justified in view of the
improved specificity and sensitivity. Minerva Foundation Institute for Medical Research and Medix Laboratories, SF-00101 Helsinki 10, Finland
FALSE-POSITIVE TESTS FOR INTRINSIC-FACTOR ANTIBODY
SIR Thompson8 reported on false-positive tests for blocking antibodies (Ab) to intrinsic factor (I.F.) in patients treated with parenteral vitamin B12. Such patients have free vitamin B12 in their sera, which disturbs the assay. This interference has been mentioned earlier as a possible source of error.91O It can be eliminated by pretreatment of the sample with coated charcoal3 or by dialysis.8 However, the problem is to find the samples to be pretreated. Dr Thompson suggests that requests for the test should always indicate whether the patient has received parenteral vitamin B12. Although this would enable us to pick out the samples to be adsorbed, it is our experience that the necessary information is very rarely obtained. ’fo detect the presence of free vitamin B12 we have modified the charcoal assay for I.F. Ab of Gottlieb et al.9 The modification also improves the reproducibility and the sensitivity. In this assay I.F. Ab are detected by their by ability to block the binding of radioactive vitamin Bla to a standard I.F. preparation. In our modified assay we make a serum control to determine the unsaturated vitamin B12-binding capacity of each sample. This enables us to pick out sera containing free vitamin Bu, because these have an apparent unsaturated binding capacity of less than 0.1 ng/ml. If such samples are positive for I.F. Ab, they are adsorbed with coated charcoal and retested. The serum control is also used to correct the results for the binding capacity of the sample. If this step is omitted9 too low results are obtained, sera lacking I.F. Ab give apparently negative results, and low titres of antibody are masked by the binding capacity of the sample. However, even when this correction had been made, we often observed a clearly higher net binding capacity of the I.F. standard in the presence of normal serum than without serum. This was apparently due to a protein effect; the additional proteins of the serum sample improved the coating and lowered the adsorption of i.F. to the charcoal. We therefore measure the binding capacity of the I.F. 1. 2. 3.
G. A. Br. med. J. 1976, ii, 106. G. A. Lancet, 1972, ii, 1197. R. H., Brownell, B. J. Neurol. Neurosurg.
MacGregor, MacGregor, Hewlett,
Psychiat. 1975, 38,
1090. 4. Scott, B. B., Losowski, M. S. Lancet, 1975, ii, 956. 5. Karlish, A. J., MacGregor, G. A. ibid. 1970, ii, 330. 6. MacGregor, G. A. ibid. 1973, i, 1133. 7. James, G. D., Neville, E., Walker, A. Am. J. Med. 1975, 59, 388. 8. Thompson, R. A. Lancet, 1976, i, 310. 9. Gottlieb, C., Lau, K.-S., Wasserman, L., R., Herbert, V. Blood, 1965, 25, 875. 10. Rothenberg, S. P., Kantha, K. R. K., Ficarra, A. J. Lab. clin. Med. 1971,
77, 476.
U. H. STENMAN*
Newmark, P., Patel, N. Blood, 1971, 38, 524. *Present address: Department of Immunology, City of Hope National Medical Center, Duarte, California 91010, U.S.A. 11.
Obituary VICTOR HORSLEY RIDDELL M.D. Cantab., F.R.C.S.
Mr Victor Riddell, honorary consultant surgeon to St. George’s Hospital, London, died on Aug. 9 at the age of 71. He was educated at Clifton, Cambridge University, and St, George’s Hospital, London, qualifying in 1930; he became F.R.c.s. 3 years later. He was appointed to the staff of St. George’s Hospital as surgeon in 1939, an appointment he held until his retirement in 1970. He travelled widely abroad as an
ambassador for British surgery, and was an active member of the International Society of Surgery, being treasurer from 1950 to 1960. He was examiner in surgery for the Universities of Birmingham, Cambridge, Leeds, and London, and he was surgical adviser to the Civil Aviation Department (Medical Branch) of the Department of Trade and Industry. H. F. A. writes: "Victor Riddell was a St. George’s Hospital man born and bred. As a resident surgical officer he was one of the pioneers of blood-transfusion; in those early days relatives had to be summoned, cross-matched--crudely, by modern standardsand bled in the casualty department. Their blood was then fed into the patient by means of a three-way syringe, which first drew up saline, then blood, and then injected the mixture into the patient. The whole procedure was done by hand and took half a day, but many lives were saved. To save time and labour, Victor Riddell later developed an electrically driven rotary pump to dispense with manual administration of the blood; it had two speeds, splendidly labelled ’petite vitesse’and ’grande vitesse’. "In his early days Victor Riddell had a hard struggle, but once on the staff of St. George’s he immediately began to make his mark. During the 1939-45 war he was one of the few who bore the brunt of the bombing raids on London, working day and night at the height of the Blitz. His main contributions to surgical knowledge were on thyroid disease and breast surgery. He was one of the first to advocate routine identification of the recurrent laryngeal nerves in all patients, and he spent much time in teaching his assistants this important principle. He worked out his own technique for the operation of thyroidec-
SIR,-Inflammatory lesions which begin subacutely are notoriously hard to diagnose. The case reported in detail by Dr Henriksson and his colleagues (Aug. 7, p. 317) was, for example, diagnosed only after four years had elapsed. Presumably by then, the biochemical and histological changes had altered considerably. An earlier pathological process therefore probably induced the enteropathy and polymyositis in their four patients. Sarcoidosis is occasionally associated with the coeliac the syndrome,! peripheral neuropathy,2 polymyositis,3 seven of autoimmune disorders listed by Scott and Losowski,4 s and parathyroid dysfunction.6 Sarcoid infiltration greatly raises the level of humoral and cellular immunity and it generates immune complexes.’ Systemic spread of the sarcoid agent may produce granulomas in any organ, and the local immune response partly decides which syndrome arises. Sarcoidosis possibly caused the muscle disease and enteropathy in these four cases.
St. Luke’s Hospital, Guildford, Surrey GU1
3NT
GERALD A. MACGREGOR
standard in the presence of normal serum. This modification also eliminates another possible error (i.e., adsorption of I.F. to the test tubel1). Our modified method has been in routine use for four years, Of 1000 consecutive samples tested during the past 17 months 55 were positive for I.F. Ab. 7 of these were retested due to the presence of free vitamin B12. After adsorption with haemoglobin-coated charcoal 5 were still positive, whereas 2 could be
excluded as false positives. Another advantage of the modified method is the increased sensitivity. A blocking activity of 1.5 ng/ml can be reliably measured. With the original coated-charcoal method" we used a cut-off level of 2 ng/ml, but in practice we did not detect levels below 3 ng/ml due to the artifact caused by the binding capacity of the sample. 5 of the 53 true-positive patients in our series would not have been detected by the earlier used method.9 The additional effort needed for the modified method (four tubes per assay instead of two) seems justified in view of the
improved specificity and sensitivity. Minerva Foundation Institute for Medical Research and Medix Laboratories, SF-00101 Helsinki 10, Finland
FALSE-POSITIVE TESTS FOR INTRINSIC-FACTOR ANTIBODY
SIR Thompson8 reported on false-positive tests for blocking antibodies (Ab) to intrinsic factor (I.F.) in patients treated with parenteral vitamin B12. Such patients have free vitamin B12 in their sera, which disturbs the assay. This interference has been mentioned earlier as a possible source of error.91O It can be eliminated by pretreatment of the sample with coated charcoal3 or by dialysis.8 However, the problem is to find the samples to be pretreated. Dr Thompson suggests that requests for the test should always indicate whether the patient has received parenteral vitamin B12. Although this would enable us to pick out the samples to be adsorbed, it is our experience that the necessary information is very rarely obtained. ’fo detect the presence of free vitamin B12 we have modified the charcoal assay for I.F. Ab of Gottlieb et al.9 The modification also improves the reproducibility and the sensitivity. In this assay I.F. Ab are detected by their by ability to block the binding of radioactive vitamin Bla to a standard I.F. preparation. In our modified assay we make a serum control to determine the unsaturated vitamin B12-binding capacity of each sample. This enables us to pick out sera containing free vitamin Bu, because these have an apparent unsaturated binding capacity of less than 0.1 ng/ml. If such samples are positive for I.F. Ab, they are adsorbed with coated charcoal and retested. The serum control is also used to correct the results for the binding capacity of the sample. If this step is omitted9 too low results are obtained, sera lacking I.F. Ab give apparently negative results, and low titres of antibody are masked by the binding capacity of the sample. However, even when this correction had been made, we often observed a clearly higher net binding capacity of the I.F. standard in the presence of normal serum than without serum. This was apparently due to a protein effect; the additional proteins of the serum sample improved the coating and lowered the adsorption of i.F. to the charcoal. We therefore measure the binding capacity of the I.F. 1. 2. 3.
G. A. Br. med. J. 1976, ii, 106. G. A. Lancet, 1972, ii, 1197. R. H., Brownell, B. J. Neurol. Neurosurg.
MacGregor, MacGregor, Hewlett,
Psychiat. 1975, 38,
1090. 4. Scott, B. B., Losowski, M. S. Lancet, 1975, ii, 956. 5. Karlish, A. J., MacGregor, G. A. ibid. 1970, ii, 330. 6. MacGregor, G. A. ibid. 1973, i, 1133. 7. James, G. D., Neville, E., Walker, A. Am. J. Med. 1975, 59, 388. 8. Thompson, R. A. Lancet, 1976, i, 310. 9. Gottlieb, C., Lau, K.-S., Wasserman, L., R., Herbert, V. Blood, 1965, 25, 875. 10. Rothenberg, S. P., Kantha, K. R. K., Ficarra, A. J. Lab. clin. Med. 1971,
77, 476.
U. H. STENMAN*
Newmark, P., Patel, N. Blood, 1971, 38, 524. *Present address: Department of Immunology, City of Hope National Medical Center, Duarte, California 91010, U.S.A. 11.
Obituary VICTOR HORSLEY RIDDELL M.D. Cantab., F.R.C.S.
Mr Victor Riddell, honorary consultant surgeon to St. George’s Hospital, London, died on Aug. 9 at the age of 71. He was educated at Clifton, Cambridge University, and St, George’s Hospital, London, qualifying in 1930; he became F.R.c.s. 3 years later. He was appointed to the staff of St. George’s Hospital as surgeon in 1939, an appointment he held until his retirement in 1970. He travelled widely abroad as an
ambassador for British surgery, and was an active member of the International Society of Surgery, being treasurer from 1950 to 1960. He was examiner in surgery for the Universities of Birmingham, Cambridge, Leeds, and London, and he was surgical adviser to the Civil Aviation Department (Medical Branch) of the Department of Trade and Industry. H. F. A. writes: "Victor Riddell was a St. George’s Hospital man born and bred. As a resident surgical officer he was one of the pioneers of blood-transfusion; in those early days relatives had to be summoned, cross-matched--crudely, by modern standardsand bled in the casualty department. Their blood was then fed into the patient by means of a three-way syringe, which first drew up saline, then blood, and then injected the mixture into the patient. The whole procedure was done by hand and took half a day, but many lives were saved. To save time and labour, Victor Riddell later developed an electrically driven rotary pump to dispense with manual administration of the blood; it had two speeds, splendidly labelled ’petite vitesse’and ’grande vitesse’. "In his early days Victor Riddell had a hard struggle, but once on the staff of St. George’s he immediately began to make his mark. During the 1939-45 war he was one of the few who bore the brunt of the bombing raids on London, working day and night at the height of the Blitz. His main contributions to surgical knowledge were on thyroid disease and breast surgery. He was one of the first to advocate routine identification of the recurrent laryngeal nerves in all patients, and he spent much time in teaching his assistants this important principle. He worked out his own technique for the operation of thyroidec-
