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MATERNAL DEATHS
1099 to go further into the analysis of the data possible in the formative years of the inquiry.
niques of tubal surgery give rise to such a significant difference
be advisable
in the results. This suggests that there is an anatomical basis to the problem. We hope that use of the Hulka-Clemens clip will limit the amount of tissue destruction and lead to a decrease in these symptoms. A. T. LETCHWORTH Royal Hampshire County Hospital, Winchester A. D. NOBLE
was
Welsh National School of Medicine, Department of Medical Statistics, Heath Park, Cardiff CF4 4XN.
than
R. G. NEWCOMBE HUBERT CAMPBELL IAIN CHALMERS
FATE OF 125I-LABELLED FIBRINOGEN LIVER LESIONS AND ANDROGENIC STEROID THERAPY
SiR,-The finding (Nov. 22, p. 1042) of widespread hyperplastic lesions in the livers of anasmic patients treated with anabolic steroids is an important one, which will help to focus other workers’ attention on changes in the rest of the liver in patients with discrete liver tumours. The suggestion that the term "focal nodular hyperplasia" should be used for such multiple hyperplastic foci is, however, likely to add to the existing confusion. This term is already used for another lesion, in which liver cells, bileducts, fibrous tissue, and blood-vessels form characteristic solitary or sometimes multiple nodules,’ possibly hamartomatous in nature. These, like the quite different liver-cell adenomas which are purely hepatocellular, may be found in patients taking oral contraceptives, although the nature and significance of the association is far from proven.2 Department of Histopathology, Royal Free Hospital, Pond Street, London NW3 2QG.
SIR,-We wish to present some preliminary observations of the fate of 1211-labelled autologous fibrinogen, in response to the report by Edwards and Haynes.’ We have investigated the radioactivity in leg-vein thrombi taken from two patients at necropsy who had earlier received autologous fibrinogen labelled with iodine-125. The material produced in our laboratories has been used in some 70 patients and volunteers2 and is known to have similar properties to native fibrinogen. The semilog plot, loglo% of initial blood radioactivity versus time, is linear with a half-life of 3.95 days in normal volunteers and an estimated extravascular compartment of 24-86%. A kit for the rapid preparation of this radiopharmaceutical is being developed. Autologous I25I-fibrinogen is being used in this centre in a clinical trial designed to assess the efficacy and safety of subcutaneous heparin in prophylaxis against deep-vein thrombosis. The two patients described here were "controls" in this trial, undergoing major gastric surgery and receiving 125I-fibrinogen immediately after the operation.
They were not given heparin. postoperative day patient A had a 20% increase in actiadjacent points in his left calf which persisted until death, and this was regarded as fulfilling the criteria for the presence of deep-venous thrombosis.3 He developed bronchopneumonia from which he died on the 4th postoperative day, at which time scanning showed high activity in both legs below the knees. At necropsy careful dissection of veins in both legs revealed the presence of ante-mortem thrombi, particularly within the soleal plexus and popliteal veins. Organisation of the thrombi appeared more advanced on the left side. A small peripheral pulmonary embolus was also noted. Patient B showed no evidence of venous thrombosis on leg scanning for the first 8 postoperative days. 17 days after the initial operation, a second operation was performed, and the patient progressively deteriorated, dying 9 days later from peritonitis and bronchopneumonia with multiple pulmonary emboli. Both femoral veins and On the 3rd
PETER
J. SCHEUER
MATERNAL DEATHS editorial SIR,-Your (Nov. 15, p. 963) comments on the seventh triennial Report on Confidential Enquiries into Maternal Deaths in England and Wales, covering the years 1970-72. A continuing fall in the number of deaths and in the maternal mortality-rate is recorded. During the nine years 1964—72 there were large changes in the age and parity of parturients, an increasing proportion of deliveries took place in hospital, and the Termination of Pregnancy Act 1967 came into effect. Although the report contains analyses which standardise for some of these variables, there is no assessment of the overall effect of these social and medical changes. Where the data have been standardised, real improvement seems to have been
patchy. We have standardised the mortality-rates for age and parity between 1964-66 and 1970-72 and we find that, whereas the ratio of the crude rates for "true" maternal mortality was 0.69, the S.M.R. when adjusted for age was 0.76 and when adjusted for parity was 0.77. When adjusted for age and parity simultaneously it was 0-80. It is clear, therefore, that there has been a real improvement of about 20% in maternal mortality, possibly attributable to the factors mentioned in the editorial. However, at least one-third of the observed improvement is due to the changing age and parity of the parturients. Similar effects may be due to changes in social class, and particularly in the gestational age at which abortions occur. The Department of Health no doubt has information which would allow proportional allocation of the observed fall to changes in the characteristics of pregnant women and the supposed effectiveness of medical intervention, but until this is done it cannot be said that a critical self-appraisal of the effectiveness of the work of obstetricians has been completed. We agree that this inquiry has for twenty-one years been an admirable example of critical self-appraisal, but it would now 1. Edmonson, H. A. Tumors of the Liver and Intrahepatic Bile Ducts. Atlas of Tumor Pathology; section vii, fascicle 25. Washington, 1958. 2 Anthony, P. P. Lancet, 1975, i, 685.
vity
over two
smaller veins of the left calf contained adherent ante-mortem thrombi. Sections of thrombi taken from veins in various sites in both patients were studied by autoradiography. In patient A, who had been given labelled autologous fibrinogen 4 days before death, radioactivity was exclusively attached to fibrinogen and arranged in the form of strands. Edwards and Haynes’ found that at 60 hours the "majority of radioactivity was in relation to white blood-cells", and it must be recalled that these workers had used homologous commercially produced fibrinogen.
The purpose of our study has been to demonstrate the precise localisation of autologous fibrinogen produced in our laboratory, when taken up in a fresh thrombus. Fibrinogen obtained from commercial sources is not recommended for use in metabolic studies, being not reproducible between batches4 and containing degraded and denatured material as well as free iodine. McFarlane’ suggested that
fibrin/fibrinogen degradation products
are
phagocytosed by
cellular components in, or close to, the intravascular compartment. This pinocytosis by polymorphonuclear leucocytes has been observed experimentally by Bocci and his colleagues6 for other plasma-proteins, and there is positive chemotaxis of these cells for components of plasmin-digested fibrinogen.’ The degraded material present in the fibrinogen preparation administered to the patient of Edwards and Haynes, and certainly found in the second of our two patients at auto-radio1. 2.
Edwards, D. H., Haynes, D. W. Lancet, 1974, ii, 220. Hawker, R. J., Hawker, L. M. Unpublished.
3. Kakkar, V. V. m Thromboembolism: Diagnosis and Treatment (edited by V. V. Kakkar and A. J. Jouhar); p. 101. Edinburgh, 1972. 4. Hickman, J. A. Br. J. Hæmat. 1971, 20, 611. 5. McFarlane, A. S. Clin. Sci. 1964, 26, 415. 6. Bocci, V., Masti, L., Pacini, A., Viti, A. Exp. Cell Res. 1968, 52, 129. 7. McKenzie, R., Pepper, D. S., Kay, A. B. Thromb. Res. 1975, 6, 1.
niques of tubal surgery give rise to such a significant difference
be advisable
in the results. This suggests that there is an anatomical basis to the problem. We hope that use of the Hulka-Clemens clip will limit the amount of tissue destruction and lead to a decrease in these symptoms. A. T. LETCHWORTH Royal Hampshire County Hospital, Winchester A. D. NOBLE
was
Welsh National School of Medicine, Department of Medical Statistics, Heath Park, Cardiff CF4 4XN.
than
R. G. NEWCOMBE HUBERT CAMPBELL IAIN CHALMERS
FATE OF 125I-LABELLED FIBRINOGEN LIVER LESIONS AND ANDROGENIC STEROID THERAPY
SiR,-The finding (Nov. 22, p. 1042) of widespread hyperplastic lesions in the livers of anasmic patients treated with anabolic steroids is an important one, which will help to focus other workers’ attention on changes in the rest of the liver in patients with discrete liver tumours. The suggestion that the term "focal nodular hyperplasia" should be used for such multiple hyperplastic foci is, however, likely to add to the existing confusion. This term is already used for another lesion, in which liver cells, bileducts, fibrous tissue, and blood-vessels form characteristic solitary or sometimes multiple nodules,’ possibly hamartomatous in nature. These, like the quite different liver-cell adenomas which are purely hepatocellular, may be found in patients taking oral contraceptives, although the nature and significance of the association is far from proven.2 Department of Histopathology, Royal Free Hospital, Pond Street, London NW3 2QG.
SIR,-We wish to present some preliminary observations of the fate of 1211-labelled autologous fibrinogen, in response to the report by Edwards and Haynes.’ We have investigated the radioactivity in leg-vein thrombi taken from two patients at necropsy who had earlier received autologous fibrinogen labelled with iodine-125. The material produced in our laboratories has been used in some 70 patients and volunteers2 and is known to have similar properties to native fibrinogen. The semilog plot, loglo% of initial blood radioactivity versus time, is linear with a half-life of 3.95 days in normal volunteers and an estimated extravascular compartment of 24-86%. A kit for the rapid preparation of this radiopharmaceutical is being developed. Autologous I25I-fibrinogen is being used in this centre in a clinical trial designed to assess the efficacy and safety of subcutaneous heparin in prophylaxis against deep-vein thrombosis. The two patients described here were "controls" in this trial, undergoing major gastric surgery and receiving 125I-fibrinogen immediately after the operation.
They were not given heparin. postoperative day patient A had a 20% increase in actiadjacent points in his left calf which persisted until death, and this was regarded as fulfilling the criteria for the presence of deep-venous thrombosis.3 He developed bronchopneumonia from which he died on the 4th postoperative day, at which time scanning showed high activity in both legs below the knees. At necropsy careful dissection of veins in both legs revealed the presence of ante-mortem thrombi, particularly within the soleal plexus and popliteal veins. Organisation of the thrombi appeared more advanced on the left side. A small peripheral pulmonary embolus was also noted. Patient B showed no evidence of venous thrombosis on leg scanning for the first 8 postoperative days. 17 days after the initial operation, a second operation was performed, and the patient progressively deteriorated, dying 9 days later from peritonitis and bronchopneumonia with multiple pulmonary emboli. Both femoral veins and On the 3rd
PETER
J. SCHEUER
MATERNAL DEATHS editorial SIR,-Your (Nov. 15, p. 963) comments on the seventh triennial Report on Confidential Enquiries into Maternal Deaths in England and Wales, covering the years 1970-72. A continuing fall in the number of deaths and in the maternal mortality-rate is recorded. During the nine years 1964—72 there were large changes in the age and parity of parturients, an increasing proportion of deliveries took place in hospital, and the Termination of Pregnancy Act 1967 came into effect. Although the report contains analyses which standardise for some of these variables, there is no assessment of the overall effect of these social and medical changes. Where the data have been standardised, real improvement seems to have been
patchy. We have standardised the mortality-rates for age and parity between 1964-66 and 1970-72 and we find that, whereas the ratio of the crude rates for "true" maternal mortality was 0.69, the S.M.R. when adjusted for age was 0.76 and when adjusted for parity was 0.77. When adjusted for age and parity simultaneously it was 0-80. It is clear, therefore, that there has been a real improvement of about 20% in maternal mortality, possibly attributable to the factors mentioned in the editorial. However, at least one-third of the observed improvement is due to the changing age and parity of the parturients. Similar effects may be due to changes in social class, and particularly in the gestational age at which abortions occur. The Department of Health no doubt has information which would allow proportional allocation of the observed fall to changes in the characteristics of pregnant women and the supposed effectiveness of medical intervention, but until this is done it cannot be said that a critical self-appraisal of the effectiveness of the work of obstetricians has been completed. We agree that this inquiry has for twenty-one years been an admirable example of critical self-appraisal, but it would now 1. Edmonson, H. A. Tumors of the Liver and Intrahepatic Bile Ducts. Atlas of Tumor Pathology; section vii, fascicle 25. Washington, 1958. 2 Anthony, P. P. Lancet, 1975, i, 685.
vity
over two
smaller veins of the left calf contained adherent ante-mortem thrombi. Sections of thrombi taken from veins in various sites in both patients were studied by autoradiography. In patient A, who had been given labelled autologous fibrinogen 4 days before death, radioactivity was exclusively attached to fibrinogen and arranged in the form of strands. Edwards and Haynes’ found that at 60 hours the "majority of radioactivity was in relation to white blood-cells", and it must be recalled that these workers had used homologous commercially produced fibrinogen.
The purpose of our study has been to demonstrate the precise localisation of autologous fibrinogen produced in our laboratory, when taken up in a fresh thrombus. Fibrinogen obtained from commercial sources is not recommended for use in metabolic studies, being not reproducible between batches4 and containing degraded and denatured material as well as free iodine. McFarlane’ suggested that
fibrin/fibrinogen degradation products
are
phagocytosed by
cellular components in, or close to, the intravascular compartment. This pinocytosis by polymorphonuclear leucocytes has been observed experimentally by Bocci and his colleagues6 for other plasma-proteins, and there is positive chemotaxis of these cells for components of plasmin-digested fibrinogen.’ The degraded material present in the fibrinogen preparation administered to the patient of Edwards and Haynes, and certainly found in the second of our two patients at auto-radio1. 2.
Edwards, D. H., Haynes, D. W. Lancet, 1974, ii, 220. Hawker, R. J., Hawker, L. M. Unpublished.
3. Kakkar, V. V. m Thromboembolism: Diagnosis and Treatment (edited by V. V. Kakkar and A. J. Jouhar); p. 101. Edinburgh, 1972. 4. Hickman, J. A. Br. J. Hæmat. 1971, 20, 611. 5. McFarlane, A. S. Clin. Sci. 1964, 26, 415. 6. Bocci, V., Masti, L., Pacini, A., Viti, A. Exp. Cell Res. 1968, 52, 129. 7. McKenzie, R., Pepper, D. S., Kay, A. B. Thromb. Res. 1975, 6, 1.