179 may result in
lower
a
frequency
of sister-chromatid
ex-
changes. New York State Institute for Basic Research in Mental Retardation, Staten Island, N.Y. 10314, U.S.A.
LEMUEL A. EVANS EDMUND C. JENKINS.
GLUTEN-FREE DIET
SIR,—Ihave followed this correspondence with interest. My wife has been on such a diet for about two years, and, in our experience, Mr Hunt (July 19, p. 133) is absolutely right. The only problem my wife has is at those " stand up" parties ; she sticks to crisps and peanuts! Seriously, the diet is not rigorous if approached sensibly. However, above all, it is something positive that can be done by multiple-sclerosis sufferers. Even if the cynics say it doesn’t work, at least the patient is doing something which others suggest is of considerable use; in any case, the diet can do no harm. Frenchay Hospital,
JAMES BRIGGS.
Bristol BS16 1LE.
HEPATITIS-B ANTIGENÆMIA ASSOCIATED WITH ACTIVE CHRONIC HEPATITIS AND MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS
SIR,-Brzosko et al. found clironic hepatitis with persistent hepatitis-B antigenaemia in eighteen children with various types of glomerulonephritis. We studied a 33-yearold patient with HBsAg and active chronic hepatitis associated with mesangioproliferative glomerulonephritis. The patient was admitted to hospital with a 1-month history of increasing weakness, peripheral oedema, and dark urine.
Blood-pressure
was
170/100
mm.
Hg; serum-glutamic-
oxaloacetic-transaminase 70 l.u.; serum-glutamic pyruvictransaminase 85 l.u.; sulphabromophthalein sodium was retained for longer than normal; the serum contained HBsAg, but no antibodies; bilirubin was 1-60 mg. per 100 ml. Active chronic hepatitis was diagnosed after examination of a liver-biopsy specimen. We also found microhsematuria, cylindruria, and unselective proteinuria (2 g. per 24 hours). Glomerular filtration was 70 ml. per minute, and serum-complement (C3 and C4) levels were lower than normal. Serum IgG was increased and urinary fibrin-degradation products were present. Light and electron microscopic examination of a percutaneous renal-biopsy specimen showed no basal-membrane lesions but there were mesangial deposits and proliferation. Immunohistochemistry showed segmentary subendothelial deposits of IgG and IgM, widespread and generalised mesangial IgA deposits, positive segmentary subendothelial immunofluorescence of lqC and C4 complement deposits, and diffuse and generalised subendothelial mesangial deposits of C3. There was HBAg in the
glomerular mesangium. Immunohistochemical evidence seemed to suggest that a was involved in the pathogenesis of the disease. Unlike other reported cases of glomerulonephritis associated with hepatitis-B antigenæmia,1-5 our patient had mesangioproliferative glomerulo-
circulating immune complex
1.
Combes, B., Stastny, P., Shorey, J., Eigenbrodt, E. H., Barrera, A., Hull, A. R., Carter, N. W. Lancet, 1971, ii, 234. 2. Brzosko, W. J., Krawczyński, K., Nazarewicz, T., Morzycka, M., Nowoslawski, A. ibid. 1974, ii, 477. 3. Kneiser, M. R., Jenis, E. H., Lawenthal, D. T., Bancrott, W. H., Burns, W., Shalhoub, R. Archs Path. 1974, 97, 193. 4. Blaker, F., Hellwege, H. H., Kramer, U., Thoenes, W. Lancet, 1974, ii, 955. 5. Bajtai, G., Ambrus, M., Paál, M., Nagy, J., Deák, G. Y. ibid. 1975, i, 102.
nephritis.
The
histological type may have
been determined
by the nature of immune complexes and type of immunoglobulin involved. We believe that serum and glomerular HBsAg should be sought in glomerulonephritis of all ’ histological types.
Cattedra di Nefrologia Medica, University of Turin, Italy.
AMINOACIDS, INSULIN,
P. G. R. A.
STRATTA CAMUSSI RAGNI VERCELLONE.
AND HEPATIC
COMA
SIR,-The hypothesis put forward by Professor Munro colleagues1 to account for the coma which often develops in patients with acute liver failure suggests that and his
the hyperinsulinsemia in this condition causes excessive removal of the branched-chain aminoacids by the muscles, thus reducing their concentrations in the blood and their competition with tryptophan for the carrier mechanism which transports them into the brain. Tryptophan entry is therefore increased and this leads to an excessive production of 5-hydroxytryptamine in the brain. Curzon et al .2Z believe that a different mechanism also influences the entry of tryptophan into the brain; they believe that changes in the level of free tryptophan in the blood have a dominant effect in controlling its entry. Our findings, obtained from work done on rabbits and rats over the past few years, may be of interest. (1) When a high level of insulin in the circulating blood (200-300 lLU per ml.) is maintained over a period of 2 hours the concentration of the branched-chain aminoacids in the plasma is reduced to a third and the level of free tryptophan to a half.3 (2) At comparable concentrations of tryptophan, free in the plasma, this raised level of insulin in the circulation (which is as high as any likely to occur in acute hepatic failure) more than RELATIVE EFFECTIVENESS OF RAISED BLOOD LEVELS OF VARIOUS NEUTRAL AMINOACIDS AS INHIBITORS OF ENTRY OF L-TRYPTOPHAN INTO BRAIN
doubles the rate of entry of tryptophan into the brain. This increased entry we believe to be due to an increase in the activity of the transport mechanism that carries this aminoacid into the brain. (3) In order to reduce the entry of tryptophan into the brain by 50% the concentration of a branched-chain aminoacid in the circulation has to be raised some ten times above normal but that of phenylalanine only four times(see accompanying table). Similar inhibitions are produced by raised levels of other aromatic aminoacids. 4,5 However, competition between these aminoacids is unlikely to be of great importance at normal blood levels. (4) The entry rate into the brain of all those aminoacids normally present in protein is proportional to their blood levels Munro, H. N., Fernstrom, J. D., Wurtman, R. J. Lancet, 1975, i, 722. Curzon, G., Knott, P. J., Murray-Lyon, I. M., Record, C. O., Williams, R. ibid. i, 1092. 3. Daniel, P. M., Love, E. R., Moorhouse, S. R., Pratt, O. E. Unpublished. 4. Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. Psychol. Med. 1974, 4, 262. 5. Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E., Wilson, P. J. Physiol. 1974, 237, 22P.
1. 2.
lower
a
frequency
of sister-chromatid
ex-
changes. New York State Institute for Basic Research in Mental Retardation, Staten Island, N.Y. 10314, U.S.A.
LEMUEL A. EVANS EDMUND C. JENKINS.
GLUTEN-FREE DIET
SIR,—Ihave followed this correspondence with interest. My wife has been on such a diet for about two years, and, in our experience, Mr Hunt (July 19, p. 133) is absolutely right. The only problem my wife has is at those " stand up" parties ; she sticks to crisps and peanuts! Seriously, the diet is not rigorous if approached sensibly. However, above all, it is something positive that can be done by multiple-sclerosis sufferers. Even if the cynics say it doesn’t work, at least the patient is doing something which others suggest is of considerable use; in any case, the diet can do no harm. Frenchay Hospital,
JAMES BRIGGS.
Bristol BS16 1LE.
HEPATITIS-B ANTIGENÆMIA ASSOCIATED WITH ACTIVE CHRONIC HEPATITIS AND MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS
SIR,-Brzosko et al. found clironic hepatitis with persistent hepatitis-B antigenaemia in eighteen children with various types of glomerulonephritis. We studied a 33-yearold patient with HBsAg and active chronic hepatitis associated with mesangioproliferative glomerulonephritis. The patient was admitted to hospital with a 1-month history of increasing weakness, peripheral oedema, and dark urine.
Blood-pressure
was
170/100
mm.
Hg; serum-glutamic-
oxaloacetic-transaminase 70 l.u.; serum-glutamic pyruvictransaminase 85 l.u.; sulphabromophthalein sodium was retained for longer than normal; the serum contained HBsAg, but no antibodies; bilirubin was 1-60 mg. per 100 ml. Active chronic hepatitis was diagnosed after examination of a liver-biopsy specimen. We also found microhsematuria, cylindruria, and unselective proteinuria (2 g. per 24 hours). Glomerular filtration was 70 ml. per minute, and serum-complement (C3 and C4) levels were lower than normal. Serum IgG was increased and urinary fibrin-degradation products were present. Light and electron microscopic examination of a percutaneous renal-biopsy specimen showed no basal-membrane lesions but there were mesangial deposits and proliferation. Immunohistochemistry showed segmentary subendothelial deposits of IgG and IgM, widespread and generalised mesangial IgA deposits, positive segmentary subendothelial immunofluorescence of lqC and C4 complement deposits, and diffuse and generalised subendothelial mesangial deposits of C3. There was HBAg in the
glomerular mesangium. Immunohistochemical evidence seemed to suggest that a was involved in the pathogenesis of the disease. Unlike other reported cases of glomerulonephritis associated with hepatitis-B antigenæmia,1-5 our patient had mesangioproliferative glomerulo-
circulating immune complex
1.
Combes, B., Stastny, P., Shorey, J., Eigenbrodt, E. H., Barrera, A., Hull, A. R., Carter, N. W. Lancet, 1971, ii, 234. 2. Brzosko, W. J., Krawczyński, K., Nazarewicz, T., Morzycka, M., Nowoslawski, A. ibid. 1974, ii, 477. 3. Kneiser, M. R., Jenis, E. H., Lawenthal, D. T., Bancrott, W. H., Burns, W., Shalhoub, R. Archs Path. 1974, 97, 193. 4. Blaker, F., Hellwege, H. H., Kramer, U., Thoenes, W. Lancet, 1974, ii, 955. 5. Bajtai, G., Ambrus, M., Paál, M., Nagy, J., Deák, G. Y. ibid. 1975, i, 102.
nephritis.
The
histological type may have
been determined
by the nature of immune complexes and type of immunoglobulin involved. We believe that serum and glomerular HBsAg should be sought in glomerulonephritis of all ’ histological types.
Cattedra di Nefrologia Medica, University of Turin, Italy.
AMINOACIDS, INSULIN,
P. G. R. A.
STRATTA CAMUSSI RAGNI VERCELLONE.
AND HEPATIC
COMA
SIR,-The hypothesis put forward by Professor Munro colleagues1 to account for the coma which often develops in patients with acute liver failure suggests that and his
the hyperinsulinsemia in this condition causes excessive removal of the branched-chain aminoacids by the muscles, thus reducing their concentrations in the blood and their competition with tryptophan for the carrier mechanism which transports them into the brain. Tryptophan entry is therefore increased and this leads to an excessive production of 5-hydroxytryptamine in the brain. Curzon et al .2Z believe that a different mechanism also influences the entry of tryptophan into the brain; they believe that changes in the level of free tryptophan in the blood have a dominant effect in controlling its entry. Our findings, obtained from work done on rabbits and rats over the past few years, may be of interest. (1) When a high level of insulin in the circulating blood (200-300 lLU per ml.) is maintained over a period of 2 hours the concentration of the branched-chain aminoacids in the plasma is reduced to a third and the level of free tryptophan to a half.3 (2) At comparable concentrations of tryptophan, free in the plasma, this raised level of insulin in the circulation (which is as high as any likely to occur in acute hepatic failure) more than RELATIVE EFFECTIVENESS OF RAISED BLOOD LEVELS OF VARIOUS NEUTRAL AMINOACIDS AS INHIBITORS OF ENTRY OF L-TRYPTOPHAN INTO BRAIN
doubles the rate of entry of tryptophan into the brain. This increased entry we believe to be due to an increase in the activity of the transport mechanism that carries this aminoacid into the brain. (3) In order to reduce the entry of tryptophan into the brain by 50% the concentration of a branched-chain aminoacid in the circulation has to be raised some ten times above normal but that of phenylalanine only four times(see accompanying table). Similar inhibitions are produced by raised levels of other aromatic aminoacids. 4,5 However, competition between these aminoacids is unlikely to be of great importance at normal blood levels. (4) The entry rate into the brain of all those aminoacids normally present in protein is proportional to their blood levels Munro, H. N., Fernstrom, J. D., Wurtman, R. J. Lancet, 1975, i, 722. Curzon, G., Knott, P. J., Murray-Lyon, I. M., Record, C. O., Williams, R. ibid. i, 1092. 3. Daniel, P. M., Love, E. R., Moorhouse, S. R., Pratt, O. E. Unpublished. 4. Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E. Psychol. Med. 1974, 4, 262. 5. Baños, G., Daniel, P. M., Moorhouse, S. R., Pratt, O. E., Wilson, P. J. Physiol. 1974, 237, 22P.
1. 2.
