201 the antibiotic was given, but faeces were not cultured at that time. A week later the third abscess was drained. No further infection developed. The ulcers began to heal, and 23 days after admission the patient was discharged. Chemotherapy was given for 4 weeks. The most likely sequence of events is that during a gastroenteritis caused by S. heidelberg a bacteraemic phase occurred. A thrombophlebitis was developing at that time, and the bacteria were trapped in the saphenous vein giving rise to the abscesses.
I thank Mr J. E.
Trapnell for his permission to
report this
case.
Public Health Laboratory, Church Lane,
Heavitree,
J. B. KURTZ
Exeter EX2 5AD.
ESCHERICHIA COLI K1
StR,-Bacon and his colleagues’ noted that agglutination tests on
strains of Escherichia coli indicated the presence of K 1
antigen, but this finding was not confirmed by immunoelectrophoresis. In a study which we have been carrying out on the relationship between E. coli Kl antigen and the group-B polysaccharide of Neisseria meningitidis, we have found that it may be difficult to demonstrate antigens in conventional systems. Other workers2 3 have shown that group-B N. meningitidis and E. coli 07:Kl(L):NM share a heat-labile antigen, and in immunodiffusion experiments Grados and Ewing2 showed a line of precipitation between the E. coli OK antiserum and an extract of group-B N. meningitidis. Kasper et al. showed that
molarity of electrolyte in the gel, the reaction became more pronounced, until finally, in agarose gel made with distilled water, not only was there a strong reaction between Kl antigen and Kl antiserum but there was also a reaction of identify between Kl antiserum and pure-group-B meningococcal polysaccharide (see figure). These results not only confirm the immunochemical identity of group-B meningococcal polysaccharide with the Klantigen of E. coli but also explain why the reaction between rabbit antiserum to the KI antigen and Kl and group-B polysaccharides may not have been seen previously in gels because of their electrolyte content. It might also be significant that Kl antisera produced in rabbits are very variable: the serum used in these studies is the most reactive that we have seen. Preliminary experiments show that by using dilute buffer the reaction between pure group-B meningococcal polysaccharide and Kl or group-B meningococcal antiserum in counterimmunoelectrophoresis is enhanced to a degree similar to that seen in ordinary immunodiffusion. This finding has obvious implications for those working with "difficult" antigen/antibody systems.
Group-B meningococcal polysaccharide and goat antiserum group-B N. meningitidis were provided by Dr E. Gotschlich. Department of Laboratory Medicine, Ruchill Hospital,
Glasgow G20
to
R. J. FALLON
9NB.
Research Department, Wellcome Reagents Limited, Wellcome Research Laboratories,
Beckenham,
M. B. MCILLMURRAY
Kent BR3 3BS.
HEREDITARY RECURRENT HÆMATURIA
SIR,-We have seen three
cases
similar
to
the
one
described
by Dr Argianas and others (Oct. 11, p. 715), in which persons of the same family had relapsing painless haematuria. Nothing was found on detailed laboratory and X-ray examinations (including angiography). Nevertheless, follow-up was suggested and one year later epithelioma of the left kidney was detected in
one
of them. Before haematuria is characterised
as
idio-
pathic investigations must be repeated so that other causes which might be missed in the first instance can be definitely excluded.
immunodiffusion using 1% agarose gel in distilled
water.
1. Group-B meningococcal polysaccharide. 2. K1 antigen. 3. Goat antiserum to group-B N. meningitidis. 4. Antiserum to E. coli 07:K1(L)NM.
the
group-specific polysaccharide of group-B N. meningitidis polymer of N-acetyl neuraminic acid immunochemically similar to the polysaccharide K antigen of E. coli 07:K1(L):NM. In diffusion experiments using rabbit antiserum to N. meningitidis groulrB antigen these workers showed that E. coli K1(L) antigen gave a reaction of identity with all of four different lots of N. meningitidis group-B polysaccharide. In view of these findings one of us (M.B.M.) prepared a rabbit antiserum to E. coli Kl antigen. This serum agglutinated both E. coli 07:Kl(L):NM and group-B N. meningitidis. In conventional immunodiffusion tests using 1% agarose in saline (39 g/1), only a weak line developed between Kl antiserum and crudely purified Kl antigen. However, if immunodiffusion tests were modified by decreasing the
was a
1
Bacon, C. J , Kenna, A. P., Ingham, H. R., Gross, R. J., Rowe, B. Lancet, 1975, ii, 1091. 2. Grades, O., Ewing, W. H. J. infect. Dis. 1970, 122, 100. 3 Kasper, D. L., Winkelhake, J. L., Zollinger, W. D., Brandt, B. L., Artenstein, M. S. J. Immun. 1973, 110, 262.
Department of Urology, State General Hospital, of Athens, Greece
C. DIMOPOULOS N. PANAYOTIDES
ŒDEMA IN COR PULMONALE
SIR,-It is twenty years and
more
since I first
wrote
about
pulmonary hypertension in patients with congenital and acquired heart-disease and chronic lung disease: you might reasonably assume that senility has made me foolish enough to comment critically about your comprehensive editorial (Dec. 27, p. 1289). However, I would like to take you to task over the statement that "Despite a raised pulmonary arterial pressure the cardiac output is usually normal, so that the pulmonary vascular resistance is very high". The pulmonary vascular resistance and the pulmonary arterial blood-pressure are raised in anoxic cor pulmonale! but usually not very high when compared with levels seen in patients with congenital septal defects2 and shunt reversal with idiopathic3 or thromboembolic4 pulmonary hypertension, or quite commonly with mitral stenosis. 1 also think that you have put the cart before the horse, and I would suggest that what you were trying to say was: "Despite an increased pulmonary vascular resistance, priWhitaker, W. Q. Jl Med. 1954, 23, 57. Heath, D., Whitaker, W. Br. Heart J. 1957, 19, 327. 3. Thadani, U., Burrow, C., Whitaker, W., Heath, D. Q. Jl
1. 2.
133. 4.
Olley, P. M., Whitaker, W. Br. Heart J. 1967, 29, 369.
Med.
1975, 44,
202 from anoxia, the cardiac output is usually normal so that the pulmonary arterial blood-pressure is raised"-but not usually to the levels seen in patients with the other conditions I have mentioned.
marily
Department of Cardiology, General Infirmary,
W. WHITAKER
Leeds 1
THYROID-HORMONE LEVELS IN PROTEIN-CALORIE MALNUTRITION
SiR,—Dr Ingenbleek and Professor Beckers (Nov. 1, p. 845) described very low serum-total-triiodothyronine (T3) concentrations in severe malnutrition and implied that these were due to decreased peripheral (e.g., hepatic) conversion of thyroxine (T4) and T3 as has been postulated to explain a similar finding in cirrhosis of the liver.’2 They also suggested that a defect in the feedback mechanism might explain the observed lack of a negative correlation between serum-total-T3 and serum-
thyroid-stimulating-hormone (T.S.H.) concentrations. We believe that decreased circulating levels of the three thyroxinebinding proteins (thyroxine-binding globulin [T.B.G.], thyroxine-binding prealbumin [T.B.P.A.], and albumin) played a bigger part than the authors suggested and may in fact have been the main factor involved. Typical mean serum-concentrations
of total T3, total T4, T.B.G., T.B.P.A., and albumin for the malnourished children described are 25%, 40%,3 56%,3 29%,4 and 53%4 of the control mean values. At a physiological pH, T.B.G., T.B.P.A., and albumin bind respectively 78%, 9%, and 13% of serum-T3 and 72%, 19%, and 9% of serum-T4.’ From these Chopra, I. J., Solomon, D. H., Chopra, U., Young, R. T., Guadalupe, C. T. J. clin. Endocr. Metab. 1974, 39, 501. 2. Nomura, S., Pittman, C. S., Chambers, J. B., Buck, M. W., Shimizu, T. J. clin. Invest. 1975, 56, 643. 3. Ingenbleek, Y., De Nayer, Ph., De Visscher, M. J. clin. Endocr. Metab. 1974, 39, 178. 4. Ingenbleek, Y., De Visscher, M., De Nayer, Ph. Lancet, 1972, ii, 106. 5. Davis, P. J., Handwerger, B. S., Gregerman, R. I. J. clin. Invest. 1972, 51, 515. 1.
account for all of the observed fall in serum-total-T4 and for 47% of the observed 77% fall in serum-total-T3 concentration. It is only the other 30% of the decrease in serum-total-T3 concentration which may perhaps be due to decreased peripheral deiodination of T4 to T3. Furthermore, the rise in serum total T3 and T4 concentrations which occurs on refeeding can be largely accounted for by the increasing concentrations of T.B.G., T.B.P.A., and albumin344 (see figure). The authors’ observation that the maximum rise in serum-T.s.H. occurred at a time when the mean serum-total-T3 concentration was nearly normal may indicate that thyroxine-binding-protein production increased faster than T3 production, thus causing a low-serum-free-T3 concentration and hence a rise in serum-T.s.H. concentration. It may not therefore be necessary to postulate a defect in the feedback mechanism. The contribution of changes of thyroxine-binding proteins to the abnormalities of thyroid hormones which occur in malnutrition and refeeding could be clarified if the serum-free-concentrations of T3 and T4 were accurately measured.
data, decreased protein-binding could
Institute of Medical and
Veterinary Science, Adelaide, South Australia, 5000.
R. W. PAIN P. J. PHILLIPS
HOW DOES BLOOD-PRESSURE CAUSE STROKE?
SIR,-Iread with interest the hypothesis put forward by Dr (Dec. 27, p. 1283) in his admirable article on blood-pressure and strokes. However, his statement, in the section on the control of cerebral blood-flow, that the intrinsic Ross Russell
autoregulatory mechanism does not depend on vascular innervation needs fuller support. How can this fact be known for man, bearing in mind the complexity of the suggested vasodilator pathways? Indeed animal data strongly suggest the
opposite.6-8 Medical Unit, Royal Free Hospital, Pond Street, London NW3 2QG.
I. M. JAMES
METHYLDOPA AND FORGETFULNESS
SIR,-Disorders of cerebral functions (i.e., depression, disturbed sleep, unpleasant dreams, and hallucinations) have been noted as side-effects from methyldopa therapy in hypertension, but I wonder if forgetfulness has been recorded. An intelligent nursing sister aged 36 was admitted with a history of shortness of breath, dizziness, and feeling faint while hurrying to catch a bus on the morning of admission. The only significant abnormality was raised blood-pressure, ranging between 170/110 and 180/120 mm Hg. The usual investigations proved normal. Methyldopa (’Aldomet’) 250 mg twice a day was started. The dose was increased to 250 mg three times a day 4 days later. Triamterene and hydrochlorothiazide (’Dyazide’), one tablet daily, was added after a fortnight. The blood-pressure returned to normal on this treatment and she was allowed to return to work. 47 days after starting methyldopa therapy and 43 days after dose she began to be forgetful. She would walk the other end of the ward to bring an article which a patient had requested, but when she reached the cupboard she would forget what the patient had asked her to get. On another occasion she went shopping in her car, but returned home by bus without realising that she had left her car in town. Methyldopa was withdrawn and replaced by debrisoquine sulphate. Dyazide was maintained. Her memory started improving within 2 days, resulting in complete recovery in a fortnight. 6 weeks later at follow-up she confirmed no further
increasing the to
problem. ’
°
DAYS
W
OF
22
REFEEDING
Average changes in thyroid hormones and thyroxine-binding proteins infants with protein-calorie malnutrition and upon refeeding.
in
6. James, I. M., Millar, R. A., Purves, M. J. Circulation Res. 1969, 25, 7. Ponte, J., Purves, M J. J. Physiol. Lond. 1974, 237, 465. 8. James, I. M., MacDonell, L. Clin. Sci. mol. Med. 1975, 49, 465.
72.
I thank Mr J. E.
Trapnell for his permission to
report this
case.
Public Health Laboratory, Church Lane,
Heavitree,
J. B. KURTZ
Exeter EX2 5AD.
ESCHERICHIA COLI K1
StR,-Bacon and his colleagues’ noted that agglutination tests on
strains of Escherichia coli indicated the presence of K 1
antigen, but this finding was not confirmed by immunoelectrophoresis. In a study which we have been carrying out on the relationship between E. coli Kl antigen and the group-B polysaccharide of Neisseria meningitidis, we have found that it may be difficult to demonstrate antigens in conventional systems. Other workers2 3 have shown that group-B N. meningitidis and E. coli 07:Kl(L):NM share a heat-labile antigen, and in immunodiffusion experiments Grados and Ewing2 showed a line of precipitation between the E. coli OK antiserum and an extract of group-B N. meningitidis. Kasper et al. showed that
molarity of electrolyte in the gel, the reaction became more pronounced, until finally, in agarose gel made with distilled water, not only was there a strong reaction between Kl antigen and Kl antiserum but there was also a reaction of identify between Kl antiserum and pure-group-B meningococcal polysaccharide (see figure). These results not only confirm the immunochemical identity of group-B meningococcal polysaccharide with the Klantigen of E. coli but also explain why the reaction between rabbit antiserum to the KI antigen and Kl and group-B polysaccharides may not have been seen previously in gels because of their electrolyte content. It might also be significant that Kl antisera produced in rabbits are very variable: the serum used in these studies is the most reactive that we have seen. Preliminary experiments show that by using dilute buffer the reaction between pure group-B meningococcal polysaccharide and Kl or group-B meningococcal antiserum in counterimmunoelectrophoresis is enhanced to a degree similar to that seen in ordinary immunodiffusion. This finding has obvious implications for those working with "difficult" antigen/antibody systems.
Group-B meningococcal polysaccharide and goat antiserum group-B N. meningitidis were provided by Dr E. Gotschlich. Department of Laboratory Medicine, Ruchill Hospital,
Glasgow G20
to
R. J. FALLON
9NB.
Research Department, Wellcome Reagents Limited, Wellcome Research Laboratories,
Beckenham,
M. B. MCILLMURRAY
Kent BR3 3BS.
HEREDITARY RECURRENT HÆMATURIA
SIR,-We have seen three
cases
similar
to
the
one
described
by Dr Argianas and others (Oct. 11, p. 715), in which persons of the same family had relapsing painless haematuria. Nothing was found on detailed laboratory and X-ray examinations (including angiography). Nevertheless, follow-up was suggested and one year later epithelioma of the left kidney was detected in
one
of them. Before haematuria is characterised
as
idio-
pathic investigations must be repeated so that other causes which might be missed in the first instance can be definitely excluded.
immunodiffusion using 1% agarose gel in distilled
water.
1. Group-B meningococcal polysaccharide. 2. K1 antigen. 3. Goat antiserum to group-B N. meningitidis. 4. Antiserum to E. coli 07:K1(L)NM.
the
group-specific polysaccharide of group-B N. meningitidis polymer of N-acetyl neuraminic acid immunochemically similar to the polysaccharide K antigen of E. coli 07:K1(L):NM. In diffusion experiments using rabbit antiserum to N. meningitidis groulrB antigen these workers showed that E. coli K1(L) antigen gave a reaction of identity with all of four different lots of N. meningitidis group-B polysaccharide. In view of these findings one of us (M.B.M.) prepared a rabbit antiserum to E. coli Kl antigen. This serum agglutinated both E. coli 07:Kl(L):NM and group-B N. meningitidis. In conventional immunodiffusion tests using 1% agarose in saline (39 g/1), only a weak line developed between Kl antiserum and crudely purified Kl antigen. However, if immunodiffusion tests were modified by decreasing the
was a
1
Bacon, C. J , Kenna, A. P., Ingham, H. R., Gross, R. J., Rowe, B. Lancet, 1975, ii, 1091. 2. Grades, O., Ewing, W. H. J. infect. Dis. 1970, 122, 100. 3 Kasper, D. L., Winkelhake, J. L., Zollinger, W. D., Brandt, B. L., Artenstein, M. S. J. Immun. 1973, 110, 262.
Department of Urology, State General Hospital, of Athens, Greece
C. DIMOPOULOS N. PANAYOTIDES
ŒDEMA IN COR PULMONALE
SIR,-It is twenty years and
more
since I first
wrote
about
pulmonary hypertension in patients with congenital and acquired heart-disease and chronic lung disease: you might reasonably assume that senility has made me foolish enough to comment critically about your comprehensive editorial (Dec. 27, p. 1289). However, I would like to take you to task over the statement that "Despite a raised pulmonary arterial pressure the cardiac output is usually normal, so that the pulmonary vascular resistance is very high". The pulmonary vascular resistance and the pulmonary arterial blood-pressure are raised in anoxic cor pulmonale! but usually not very high when compared with levels seen in patients with congenital septal defects2 and shunt reversal with idiopathic3 or thromboembolic4 pulmonary hypertension, or quite commonly with mitral stenosis. 1 also think that you have put the cart before the horse, and I would suggest that what you were trying to say was: "Despite an increased pulmonary vascular resistance, priWhitaker, W. Q. Jl Med. 1954, 23, 57. Heath, D., Whitaker, W. Br. Heart J. 1957, 19, 327. 3. Thadani, U., Burrow, C., Whitaker, W., Heath, D. Q. Jl
1. 2.
133. 4.
Olley, P. M., Whitaker, W. Br. Heart J. 1967, 29, 369.
Med.
1975, 44,
202 from anoxia, the cardiac output is usually normal so that the pulmonary arterial blood-pressure is raised"-but not usually to the levels seen in patients with the other conditions I have mentioned.
marily
Department of Cardiology, General Infirmary,
W. WHITAKER
Leeds 1
THYROID-HORMONE LEVELS IN PROTEIN-CALORIE MALNUTRITION
SiR,—Dr Ingenbleek and Professor Beckers (Nov. 1, p. 845) described very low serum-total-triiodothyronine (T3) concentrations in severe malnutrition and implied that these were due to decreased peripheral (e.g., hepatic) conversion of thyroxine (T4) and T3 as has been postulated to explain a similar finding in cirrhosis of the liver.’2 They also suggested that a defect in the feedback mechanism might explain the observed lack of a negative correlation between serum-total-T3 and serum-
thyroid-stimulating-hormone (T.S.H.) concentrations. We believe that decreased circulating levels of the three thyroxinebinding proteins (thyroxine-binding globulin [T.B.G.], thyroxine-binding prealbumin [T.B.P.A.], and albumin) played a bigger part than the authors suggested and may in fact have been the main factor involved. Typical mean serum-concentrations
of total T3, total T4, T.B.G., T.B.P.A., and albumin for the malnourished children described are 25%, 40%,3 56%,3 29%,4 and 53%4 of the control mean values. At a physiological pH, T.B.G., T.B.P.A., and albumin bind respectively 78%, 9%, and 13% of serum-T3 and 72%, 19%, and 9% of serum-T4.’ From these Chopra, I. J., Solomon, D. H., Chopra, U., Young, R. T., Guadalupe, C. T. J. clin. Endocr. Metab. 1974, 39, 501. 2. Nomura, S., Pittman, C. S., Chambers, J. B., Buck, M. W., Shimizu, T. J. clin. Invest. 1975, 56, 643. 3. Ingenbleek, Y., De Nayer, Ph., De Visscher, M. J. clin. Endocr. Metab. 1974, 39, 178. 4. Ingenbleek, Y., De Visscher, M., De Nayer, Ph. Lancet, 1972, ii, 106. 5. Davis, P. J., Handwerger, B. S., Gregerman, R. I. J. clin. Invest. 1972, 51, 515. 1.
account for all of the observed fall in serum-total-T4 and for 47% of the observed 77% fall in serum-total-T3 concentration. It is only the other 30% of the decrease in serum-total-T3 concentration which may perhaps be due to decreased peripheral deiodination of T4 to T3. Furthermore, the rise in serum total T3 and T4 concentrations which occurs on refeeding can be largely accounted for by the increasing concentrations of T.B.G., T.B.P.A., and albumin344 (see figure). The authors’ observation that the maximum rise in serum-T.s.H. occurred at a time when the mean serum-total-T3 concentration was nearly normal may indicate that thyroxine-binding-protein production increased faster than T3 production, thus causing a low-serum-free-T3 concentration and hence a rise in serum-T.s.H. concentration. It may not therefore be necessary to postulate a defect in the feedback mechanism. The contribution of changes of thyroxine-binding proteins to the abnormalities of thyroid hormones which occur in malnutrition and refeeding could be clarified if the serum-free-concentrations of T3 and T4 were accurately measured.
data, decreased protein-binding could
Institute of Medical and
Veterinary Science, Adelaide, South Australia, 5000.
R. W. PAIN P. J. PHILLIPS
HOW DOES BLOOD-PRESSURE CAUSE STROKE?
SIR,-Iread with interest the hypothesis put forward by Dr (Dec. 27, p. 1283) in his admirable article on blood-pressure and strokes. However, his statement, in the section on the control of cerebral blood-flow, that the intrinsic Ross Russell
autoregulatory mechanism does not depend on vascular innervation needs fuller support. How can this fact be known for man, bearing in mind the complexity of the suggested vasodilator pathways? Indeed animal data strongly suggest the
opposite.6-8 Medical Unit, Royal Free Hospital, Pond Street, London NW3 2QG.
I. M. JAMES
METHYLDOPA AND FORGETFULNESS
SIR,-Disorders of cerebral functions (i.e., depression, disturbed sleep, unpleasant dreams, and hallucinations) have been noted as side-effects from methyldopa therapy in hypertension, but I wonder if forgetfulness has been recorded. An intelligent nursing sister aged 36 was admitted with a history of shortness of breath, dizziness, and feeling faint while hurrying to catch a bus on the morning of admission. The only significant abnormality was raised blood-pressure, ranging between 170/110 and 180/120 mm Hg. The usual investigations proved normal. Methyldopa (’Aldomet’) 250 mg twice a day was started. The dose was increased to 250 mg three times a day 4 days later. Triamterene and hydrochlorothiazide (’Dyazide’), one tablet daily, was added after a fortnight. The blood-pressure returned to normal on this treatment and she was allowed to return to work. 47 days after starting methyldopa therapy and 43 days after dose she began to be forgetful. She would walk the other end of the ward to bring an article which a patient had requested, but when she reached the cupboard she would forget what the patient had asked her to get. On another occasion she went shopping in her car, but returned home by bus without realising that she had left her car in town. Methyldopa was withdrawn and replaced by debrisoquine sulphate. Dyazide was maintained. Her memory started improving within 2 days, resulting in complete recovery in a fortnight. 6 weeks later at follow-up she confirmed no further
increasing the to
problem. ’
°
DAYS
W
OF
22
REFEEDING
Average changes in thyroid hormones and thyroxine-binding proteins infants with protein-calorie malnutrition and upon refeeding.
in
6. James, I. M., Millar, R. A., Purves, M. J. Circulation Res. 1969, 25, 7. Ponte, J., Purves, M J. J. Physiol. Lond. 1974, 237, 465. 8. James, I. M., MacDonell, L. Clin. Sci. mol. Med. 1975, 49, 465.
72.
