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POSTOPERATIVE PULMONARY EMBOLISM
956 found only in serum fractions which also In immunodiffusion precipitation lines of patients’ sera with hepatitis-B antibodies and with Clq showed a barely visible partial fusion. Immunohistological examination of kidney tissue showed immunoglobulin IgG (in one case also IgM and complement mune
complexes
contained
[C3]
in
a
were
HBAg.
granula. Cases of chronic hepatitis with persistent
HBAg and typical membranous glomerulonephritis are also described by Combes et al. and Knieser et al. 2 In addition to the data of Brzodsko et al., Combes et al., and Knieser et al., we found in our cases a persistence of HBAg for 1 to 2i years, and over the same time circulating immune complexes, which react with Clq and also with hepatitis-B antibodies. These findings support the view that HBAg is the antigen component of the detected soluble immune complexes. It remains an open question whether the hepatitis with intrahepatic HBAg production is the primary disease or the consequence of infections with hepatitis-B virus after onset of the renal disease. In our cases chronic persistent hepatitis was established in the initial phases of renal symptoms. No transfusions or immunosuppressive agents, which favour infection with
hepatitis-B virus,
were
given.
We agree with Professor Brzodsko and his colleagues that the high proportion of HBAg-positive chronic hepatitis in membranous glomerulonephritis should stimulate investigation of liver function and HBAg in patients with membranous nephropathy and investigation of renal function in HBAg carriers.
Universitats-Kinderklinik, Martinistrasse 52, D-2000 Hamburg.
F. BLÄKER H. H. HELLWEGE U. KRAMER W. THOENES.
NON-TREATMENT OF HYPERTENSION
SIR,-The assertion that elderly patients can gain no benefit from antihypertensive treatment could do with testing rather than making again in your columns. How does Dr Harman (Oct. 5, p. 841) know that an elevated blood-pressure in the sixties will have no avoidable effects on the end-organs during the remaining years of life? The shortcomings of Dr Fry’s evidence have been outlined by Dr Hart (Sept. 14, p. 645). The patients in the series described by Carter,3 which is sometimes quoted in this context, had all experienced a stroke, and the number over 65 was too small for any conclusion to be drawn. Many physicians have memories of elderly patients staggering under the impact of inappropriate doses of potent and unpleasant drugs. Such cautionary tales, however, are a poor reason for throwing in the sponge or for making excathedra pronouncements. If strokes and, perhaps, atherothrombotic incidents can be reduced the quality of these years may be much improved. Recent suggestions that sympathetic blockade 4 may protect against the risk of cardiac infarction makes it all the more important to carry out controlled trials in this coronary-prone group. Such trials, based on general-practice patients, are at 1.
2. 3. 4.
The Waterhouse,
Bollington, near
Macclesfield.
JOHN COOPE.
granular pattern).
The immune complexes were localised between the basement membrane and the outer epithelium. HBAg was demonstrated by F.I.T.c.-coupled homologous and heterologous antisera against HBAg in the same regions and patterns as IgG and complement
_
the moment being mounted in Newcastle upon Tyne and in Bollington. May I suggest that we wait for the evidence?
Combes, B., Stastny, P., Shorey, J., Eigenbrodt, E. H., Barrera, A., Hull, A. R., Carter, N. W. Lancet, 1971, ii, 234. Knieser, M. R., Jenis, E. H., Lawenthal, D. T., Bancroft, W. H., Burns, W., Shalhoub, R. Archs Path. 1974, 97, 193. Carter, A. B. Lancet, 1970, i, 485. Lambert, D. M. B. Br. med. J. 1944, iii, 685.
SUBCUTANEOUS HEPARIN
SIR,-You rightly raise the question (Aug. 31, p. 502): use do the advantages of prophylaxis with heparin sufficiently outweigh its possible disadvantages ?" This question is of particular interest in relation to the report of the Edinburgh multi-unit controlled trial1 This report stated that the prophylactic heparin regimen was discontinued in 11 out of 128 patients and in 7 of these the reason was concern about bleeding. Bleeding contributed to death in another patient in the heparin group. In the control group of 128 patients 1 death was due to
" In routine
massive embolism. The authors of this report commented: we believe that further studies are required to determine whether a few individual patients might be susceptible to bleeding problems with heparin ". A more appropriate conclusion from the Edinburgh experience could be that "
general application of subcutaneous heparin to patients undergoing surgery without any monitoring of its coagulation effect or measurement of heparin levels in the plasma is sufficiently hazardous to outweigh its advantages in the prevention of serious postoperative thromboembolic complications. In this department we have devised a relatively simple assay for the accurate measurement of heparin, based on its potentiating effect on the natural inhibitor anti-factor xa.2 In both obstetric and gynxcological patients we have found a wide variation in the plasma-heparin concentration in women receiving subcutaneous heparin injections of 5000 LV. 8-hourly, with peak levels varying from 0-02 i.u. per ml. to 0-8 i.u. per ml. In 4 patients with plasmaheparin levels above 0-6 LV. per ml. serious bleeding complications, particularly wound hasmatomas, have arisen. In the light of our own experience and that reported in the Edinburgh trial we consider it essential that heparin therapy should be monitored in patients undergoing major surgery, since otherwise safe and effective prophylaxis the
cannot
be achieved.
Nuffield Department of Obstetrics and Gynæcology, John Radcliffe Hospital, Headington, Oxford.
JOHN BONNAR K. W. DENSON.
POSTOPERATIVE PULMONARY EMBOLISM
SIR,-Although we wholeheartedly agree about the value heparin in the prevention of venous thrombosis and pulmonary embolism (P.E.) as reported by Lahnborg et al.,3 we believe that the reported incidence of P.E. (36% in the control group and 24% in the whole group) may not be the of
incidence. None of these patients had any preoperative perfusion or postoperative ventilation scans. Since the mean age of these patients was 62, we do not know whether the perfusion defects observed during the postoperative period were due to P.E. or to preexisting chronic obstructive pulmonary disease (C.O.P.D.). In one series, 95% of patients with emphysema had perfusion defects.44 A significant number of patients with C.O.P.D. and abnormal perfusion true
1. 2.
Lancet, July 20, 1974, p. 118. Denson, K. W. E., Bonnar, J. Thromb. Diath. hœmorrh. 1973, 30, 471.
3.
Lahnborg, G., Bergström, K., Friman, L., Lagergren, H. Lancet, 1974, i, 329. 4. Lopez-Majano, V., Tow, D. E., Wagner, H. N. J. Am. med. Ass. 1966, 197, 81.
957 can have normal chest radiographs.5 Perfusion defects did occur in 76% of geriatric patients without any detectable cause.6 So also during the immediate postoperative period after abdominal or thoracic operations, perfusion defects could be seen in more than 50% of the patients without any arteriographic evidence of P.E.7 Even segmental perfusion defects are described in C.O.P.D.8 In these circumstances, we think that the reported incidence of P.E. may be more apparent than real. scans
Department of Nuclear Medicine, Washington Hospital Center, Washington, D.C. 20010, U.S.A.
TABLE
K. P. POULOSE R. C. REBA.
OF INJURED PATIENTS INVESTIGATED DIFFUSE INTRAVASCULAR COAGULATION
I-GROUPING
*
Patients without
hxmorrhages with abnormal
FOR
tests.
TABLE II-RESULTS OF LABORATORY TESTS
ANGINA PECTORIS WITH NORMAL CORONARY ARTERIES
SIR,-Cardiac investigators are becoming increasingly of a small group of patients who, while displaying
aware
the symptoms of angina, appear to have no demonstrable lesion on coronary arteriography. Dr Richardson and his colleagues (Sept. 21, p. 677) obtained endomyocardial biopsies and found normal small vessels. Is it not speculative to draw conclusions from right ventricular histological findings about a pathological process which predominantly affects the left ventricle? St.
Mary’s Hospital, Praed Street,
R. J. VECHT.
London W2 1NY.
DEFIBRINATION AND HEAD
INJURY
of
SIR,-Our experience patients with head injury without brain-tissue destruction is largely in agreement with the report of Goodnight et awl. discussed in your editorial (June 15, p. 1206). Nevertheless, the bleeding and the positive laboratory tests indicative of diffuse intravascular coagulation (D.I.C.), in injured patients with no clinical evidence of brain-tissue damage, are worthy of comment. We are investigating the occurrence of D.I.C. in injured patients, in collaboration with the intensive-care unit and the neurosurgery department. So far 45 patients, victims of traffic and occupational accidents, without evident brain-tissue destruction, have been investigated and a common pattern is emerging. The patients are divided into three groups: group I, head injury; group n, head injury with trauma to other areas; group III, multiple trauma without head injury. The following tests were performed on admission to the intensive-care unit and on subsequent days: plateletcount ; prothrombin time (P.T.); activated partial thromboplastin time (A.P.T.T.); thrombin time (T.T.); reptilase time (R.T.) ; fibrinogen; diluted protamine-sulphate test
(P.s.); serum fibrinogen-fibrin degradation products (F.-F.R.A. Latex test, Diagen). The clinical course was complicated in 3 patients by generalised haemorrhages associated with laboratory data indicative of
D.l.C.
The laboratory tests were positive in 19 of the 42 patients without haemorrhages (table n), hyponbrinogenaemia was never observed. The P.s. test was considered positive only when strands or a gel were evident. The most frequent 5. Alderson,
P. O., Secker-Walker, R. H., Forrest, J. V. Radiology, 1974, 111, 643. 6 Freedman, S. A., Schub, H. M., Smith, E. H., Solomon, N. A. Am. Heart J. 1970, 79, 160. 7. Bryant, L. R., Spencer, P. C., Greenlaw, R. H., Prathnadi, P., Bowlin, J. W. J. thorac. cardiovasc. Surg. 1967, 53, 64. 8. Poulose, K. P., Reba, R. C., Gilday, D. L., Deland, F. H., Wagner, H. J. Br. med. J. 1970, iii, 67. 9. Goodnight, S. H., Kenoyer, G., Rapaport, S. I., Patch, M. J., Lee, J. A., Kurze, T. New Engl. J. Med. 1974, 290, 1043.
abnormalities were: thrombocytopenia, shortened A.P.T.T., increased serum F.-F.R.A., and positive P.s., with return to normal in a short time in surviving patients. Some patients had positive tests on the day of death without clinical haemorrhages. These findings indicate that generalised bleeding due to defibrination may occur in severe trauma uncomplicated by conditions considered to be triggers " of D.I.C. (shock, sepsis, &c.) and in the absence of brain-tissue destruction. Furthermore, in patients without overt bleeding, positive laboratory tests are common but transient. Their relevance to subsequent bleeding needs further assessment.
laboratory
"
Department of Hæmatology, Ospedale Maggiore Ca’ Granda, Milan, Italy.
A. STRINCHINI F. BAUDO A. M. NOSARI G. PANZACCHI F. DE CATALDO.
ASCORBIC ACID IN TREATMENT OF PRESSURE-SORES
SIR, The results obtained by Dr Taylor and his colp. 546) are very encouraging, but the dose of ascorbic acid (1000 mg. daily) may have been unnecessarily high. Our experience 1,2 indicates that, in winter illness, symptoms may be less severe in persons receiving an ascorbic-acid supplement, but a regular daily dose oi 1000 (or even 2000) mg. seems to be no more effective than
leagues (Sept. 7,
one
of 250 mg.
high intake of ascorbic acid may be needed are sick or debilitated, but we believe that prolonged supplementation with more than 100 or 200 mg. daily is inadvisable,3 unless it can be shown that higher doses are necessary to maintain tissue saturation or to achieve a satisfactory clinical response. May we also suggest that if the term double-blind is to be used in reporting a clinical trial some evidence should be presented that the active and placebo preparations were truly indistinguishable. While we have no reason to believe that the present study was inadequate in this Admittedly,
initially in
a
persons who
" respect, we know of some " double-blind trials in which it was childishly simple for both the subjects and the
1. 2. 3.
Anderson, T. W., Reid, D. B. W., Beaton, G. H. Can. med. Ass. J. 1972, 107, 503. Anderson, T. W., Suranyi, G., Beaton, G. H. ibid. 1974, 111, 31. Spero, L., Anderson, T. W. Br. med. J. 1973, iv, 354.
complexes
contained
[C3]
in
a
were
HBAg.
granula. Cases of chronic hepatitis with persistent
HBAg and typical membranous glomerulonephritis are also described by Combes et al. and Knieser et al. 2 In addition to the data of Brzodsko et al., Combes et al., and Knieser et al., we found in our cases a persistence of HBAg for 1 to 2i years, and over the same time circulating immune complexes, which react with Clq and also with hepatitis-B antibodies. These findings support the view that HBAg is the antigen component of the detected soluble immune complexes. It remains an open question whether the hepatitis with intrahepatic HBAg production is the primary disease or the consequence of infections with hepatitis-B virus after onset of the renal disease. In our cases chronic persistent hepatitis was established in the initial phases of renal symptoms. No transfusions or immunosuppressive agents, which favour infection with
hepatitis-B virus,
were
given.
We agree with Professor Brzodsko and his colleagues that the high proportion of HBAg-positive chronic hepatitis in membranous glomerulonephritis should stimulate investigation of liver function and HBAg in patients with membranous nephropathy and investigation of renal function in HBAg carriers.
Universitats-Kinderklinik, Martinistrasse 52, D-2000 Hamburg.
F. BLÄKER H. H. HELLWEGE U. KRAMER W. THOENES.
NON-TREATMENT OF HYPERTENSION
SIR,-The assertion that elderly patients can gain no benefit from antihypertensive treatment could do with testing rather than making again in your columns. How does Dr Harman (Oct. 5, p. 841) know that an elevated blood-pressure in the sixties will have no avoidable effects on the end-organs during the remaining years of life? The shortcomings of Dr Fry’s evidence have been outlined by Dr Hart (Sept. 14, p. 645). The patients in the series described by Carter,3 which is sometimes quoted in this context, had all experienced a stroke, and the number over 65 was too small for any conclusion to be drawn. Many physicians have memories of elderly patients staggering under the impact of inappropriate doses of potent and unpleasant drugs. Such cautionary tales, however, are a poor reason for throwing in the sponge or for making excathedra pronouncements. If strokes and, perhaps, atherothrombotic incidents can be reduced the quality of these years may be much improved. Recent suggestions that sympathetic blockade 4 may protect against the risk of cardiac infarction makes it all the more important to carry out controlled trials in this coronary-prone group. Such trials, based on general-practice patients, are at 1.
2. 3. 4.
The Waterhouse,
Bollington, near
Macclesfield.
JOHN COOPE.
granular pattern).
The immune complexes were localised between the basement membrane and the outer epithelium. HBAg was demonstrated by F.I.T.c.-coupled homologous and heterologous antisera against HBAg in the same regions and patterns as IgG and complement
_
the moment being mounted in Newcastle upon Tyne and in Bollington. May I suggest that we wait for the evidence?
Combes, B., Stastny, P., Shorey, J., Eigenbrodt, E. H., Barrera, A., Hull, A. R., Carter, N. W. Lancet, 1971, ii, 234. Knieser, M. R., Jenis, E. H., Lawenthal, D. T., Bancroft, W. H., Burns, W., Shalhoub, R. Archs Path. 1974, 97, 193. Carter, A. B. Lancet, 1970, i, 485. Lambert, D. M. B. Br. med. J. 1944, iii, 685.
SUBCUTANEOUS HEPARIN
SIR,-You rightly raise the question (Aug. 31, p. 502): use do the advantages of prophylaxis with heparin sufficiently outweigh its possible disadvantages ?" This question is of particular interest in relation to the report of the Edinburgh multi-unit controlled trial1 This report stated that the prophylactic heparin regimen was discontinued in 11 out of 128 patients and in 7 of these the reason was concern about bleeding. Bleeding contributed to death in another patient in the heparin group. In the control group of 128 patients 1 death was due to
" In routine
massive embolism. The authors of this report commented: we believe that further studies are required to determine whether a few individual patients might be susceptible to bleeding problems with heparin ". A more appropriate conclusion from the Edinburgh experience could be that "
general application of subcutaneous heparin to patients undergoing surgery without any monitoring of its coagulation effect or measurement of heparin levels in the plasma is sufficiently hazardous to outweigh its advantages in the prevention of serious postoperative thromboembolic complications. In this department we have devised a relatively simple assay for the accurate measurement of heparin, based on its potentiating effect on the natural inhibitor anti-factor xa.2 In both obstetric and gynxcological patients we have found a wide variation in the plasma-heparin concentration in women receiving subcutaneous heparin injections of 5000 LV. 8-hourly, with peak levels varying from 0-02 i.u. per ml. to 0-8 i.u. per ml. In 4 patients with plasmaheparin levels above 0-6 LV. per ml. serious bleeding complications, particularly wound hasmatomas, have arisen. In the light of our own experience and that reported in the Edinburgh trial we consider it essential that heparin therapy should be monitored in patients undergoing major surgery, since otherwise safe and effective prophylaxis the
cannot
be achieved.
Nuffield Department of Obstetrics and Gynæcology, John Radcliffe Hospital, Headington, Oxford.
JOHN BONNAR K. W. DENSON.
POSTOPERATIVE PULMONARY EMBOLISM
SIR,-Although we wholeheartedly agree about the value heparin in the prevention of venous thrombosis and pulmonary embolism (P.E.) as reported by Lahnborg et al.,3 we believe that the reported incidence of P.E. (36% in the control group and 24% in the whole group) may not be the of
incidence. None of these patients had any preoperative perfusion or postoperative ventilation scans. Since the mean age of these patients was 62, we do not know whether the perfusion defects observed during the postoperative period were due to P.E. or to preexisting chronic obstructive pulmonary disease (C.O.P.D.). In one series, 95% of patients with emphysema had perfusion defects.44 A significant number of patients with C.O.P.D. and abnormal perfusion true
1. 2.
Lancet, July 20, 1974, p. 118. Denson, K. W. E., Bonnar, J. Thromb. Diath. hœmorrh. 1973, 30, 471.
3.
Lahnborg, G., Bergström, K., Friman, L., Lagergren, H. Lancet, 1974, i, 329. 4. Lopez-Majano, V., Tow, D. E., Wagner, H. N. J. Am. med. Ass. 1966, 197, 81.
957 can have normal chest radiographs.5 Perfusion defects did occur in 76% of geriatric patients without any detectable cause.6 So also during the immediate postoperative period after abdominal or thoracic operations, perfusion defects could be seen in more than 50% of the patients without any arteriographic evidence of P.E.7 Even segmental perfusion defects are described in C.O.P.D.8 In these circumstances, we think that the reported incidence of P.E. may be more apparent than real. scans
Department of Nuclear Medicine, Washington Hospital Center, Washington, D.C. 20010, U.S.A.
TABLE
K. P. POULOSE R. C. REBA.
OF INJURED PATIENTS INVESTIGATED DIFFUSE INTRAVASCULAR COAGULATION
I-GROUPING
*
Patients without
hxmorrhages with abnormal
FOR
tests.
TABLE II-RESULTS OF LABORATORY TESTS
ANGINA PECTORIS WITH NORMAL CORONARY ARTERIES
SIR,-Cardiac investigators are becoming increasingly of a small group of patients who, while displaying
aware
the symptoms of angina, appear to have no demonstrable lesion on coronary arteriography. Dr Richardson and his colleagues (Sept. 21, p. 677) obtained endomyocardial biopsies and found normal small vessels. Is it not speculative to draw conclusions from right ventricular histological findings about a pathological process which predominantly affects the left ventricle? St.
Mary’s Hospital, Praed Street,
R. J. VECHT.
London W2 1NY.
DEFIBRINATION AND HEAD
INJURY
of
SIR,-Our experience patients with head injury without brain-tissue destruction is largely in agreement with the report of Goodnight et awl. discussed in your editorial (June 15, p. 1206). Nevertheless, the bleeding and the positive laboratory tests indicative of diffuse intravascular coagulation (D.I.C.), in injured patients with no clinical evidence of brain-tissue damage, are worthy of comment. We are investigating the occurrence of D.I.C. in injured patients, in collaboration with the intensive-care unit and the neurosurgery department. So far 45 patients, victims of traffic and occupational accidents, without evident brain-tissue destruction, have been investigated and a common pattern is emerging. The patients are divided into three groups: group I, head injury; group n, head injury with trauma to other areas; group III, multiple trauma without head injury. The following tests were performed on admission to the intensive-care unit and on subsequent days: plateletcount ; prothrombin time (P.T.); activated partial thromboplastin time (A.P.T.T.); thrombin time (T.T.); reptilase time (R.T.) ; fibrinogen; diluted protamine-sulphate test
(P.s.); serum fibrinogen-fibrin degradation products (F.-F.R.A. Latex test, Diagen). The clinical course was complicated in 3 patients by generalised haemorrhages associated with laboratory data indicative of
D.l.C.
The laboratory tests were positive in 19 of the 42 patients without haemorrhages (table n), hyponbrinogenaemia was never observed. The P.s. test was considered positive only when strands or a gel were evident. The most frequent 5. Alderson,
P. O., Secker-Walker, R. H., Forrest, J. V. Radiology, 1974, 111, 643. 6 Freedman, S. A., Schub, H. M., Smith, E. H., Solomon, N. A. Am. Heart J. 1970, 79, 160. 7. Bryant, L. R., Spencer, P. C., Greenlaw, R. H., Prathnadi, P., Bowlin, J. W. J. thorac. cardiovasc. Surg. 1967, 53, 64. 8. Poulose, K. P., Reba, R. C., Gilday, D. L., Deland, F. H., Wagner, H. J. Br. med. J. 1970, iii, 67. 9. Goodnight, S. H., Kenoyer, G., Rapaport, S. I., Patch, M. J., Lee, J. A., Kurze, T. New Engl. J. Med. 1974, 290, 1043.
abnormalities were: thrombocytopenia, shortened A.P.T.T., increased serum F.-F.R.A., and positive P.s., with return to normal in a short time in surviving patients. Some patients had positive tests on the day of death without clinical haemorrhages. These findings indicate that generalised bleeding due to defibrination may occur in severe trauma uncomplicated by conditions considered to be triggers " of D.I.C. (shock, sepsis, &c.) and in the absence of brain-tissue destruction. Furthermore, in patients without overt bleeding, positive laboratory tests are common but transient. Their relevance to subsequent bleeding needs further assessment.
laboratory
"
Department of Hæmatology, Ospedale Maggiore Ca’ Granda, Milan, Italy.
A. STRINCHINI F. BAUDO A. M. NOSARI G. PANZACCHI F. DE CATALDO.
ASCORBIC ACID IN TREATMENT OF PRESSURE-SORES
SIR, The results obtained by Dr Taylor and his colp. 546) are very encouraging, but the dose of ascorbic acid (1000 mg. daily) may have been unnecessarily high. Our experience 1,2 indicates that, in winter illness, symptoms may be less severe in persons receiving an ascorbic-acid supplement, but a regular daily dose oi 1000 (or even 2000) mg. seems to be no more effective than
leagues (Sept. 7,
one
of 250 mg.
high intake of ascorbic acid may be needed are sick or debilitated, but we believe that prolonged supplementation with more than 100 or 200 mg. daily is inadvisable,3 unless it can be shown that higher doses are necessary to maintain tissue saturation or to achieve a satisfactory clinical response. May we also suggest that if the term double-blind is to be used in reporting a clinical trial some evidence should be presented that the active and placebo preparations were truly indistinguishable. While we have no reason to believe that the present study was inadequate in this Admittedly,
initially in
a
persons who
" respect, we know of some " double-blind trials in which it was childishly simple for both the subjects and the
1. 2. 3.
Anderson, T. W., Reid, D. B. W., Beaton, G. H. Can. med. Ass. J. 1972, 107, 503. Anderson, T. W., Suranyi, G., Beaton, G. H. ibid. 1974, 111, 31. Spero, L., Anderson, T. W. Br. med. J. 1973, iv, 354.