677 the immune response of the host, these observations suggest that, besides assessment of H.B.V. markers, lymphocyte function should also be evaluated before any immunosuppressive treatment is started, so that patients with impaired lymphocyte response might be selected for immunostimulant therapy. This work was supported by grants from Consiglio Nazionale delle Ricerche (Rome), Progetto Finalizzato Virus, contract no. 77.00308.84.
G. PASTORE P. DENTICO R. BUONGIORNO G. ANGARANO O. SCHIRALDI
Infectious Diseases Clinic, Department of Clinical Immunology, and II Medical Clinic,
responses. However, at F.u. doses 2.00 g/ml/day there five objective tumour regressions in the ten patients treated. Four responding patients had colorectal carcinoma, and one had gastric carcinoma. We believe that allopurinol may modulate F.u. toxicity in man, allowing a two-fold increase in dose. Tumour response does not seem to be prevented by concurrent administration of allopurinol. We are now investigating the use of intravenous allopurinol and the biochemical mechanisms of allopurinol modulation of the F.u. response in man. tumour were
Ludwig Institute for Cancer Research, University of Sydney, Sydney, New South Wales 2006, Australia
A. TURSI
University of Bari Medical School, 70124 Bari, Italy
M. P. LORIA
Department of Medical Oncology, Prince Henry’s Hospital, Melbourne, Victoria
ALLOPURINOL MODULATION OF HIGH-DOSE FLUOROURACIL TOXICITY
SIR,-Fluorouracil (F.u.) causes temporary tumour regression in approximately 150 of patients with advanced gastrointestinal cancer. Several schedules of drug administration have been used with no clear advantage having been demonstrated.’ However, responses are more common in patients who have drug toxicity, suggesting a steep dose-response curve.2 The maximum tolerated daily dose of F.U. given by infusion has been 30mg/kg/day (1-1-1-2g g at 35 mg F.u./kg/day, seven out of eight patients had severe stomatitis.3 Oxypurinol, the in-vivo active metabolite of allopurinol, is a strong inhibitor of orotate phosphoribosyltransferase4 and a weak inhibitor of thymidine phosphorylase,5 two of the three enzymes which activate F.u. The toxicity of F.u. in mice is reduced by concurrent allopurinol administration, presumably because pathways activating F.u. in normal tissue are blocked.6 We have used F.u. infusions and concurrent allopurinol in thirteen patients with advanced cancer (colorectal in ten cases, ovanan in one, gastric in one, prostatic in one). Patients received allopurinol, 300 mg three times a day by mouth on days 1-6 with 2 litres of normal saline i.v. daily. F.u. was given, as a 24 h i.v. infusion on days 2-6 in the saline. The first three patients received 1 g F.u./m2/day x 5 and doses were then increased in these patients, and in new patients, to 1-5, 2.0, 225, 2.5, and 2.9 g F.u./m day x 5; the number of patients treated at these dose levels were three, three, eight, one, and one, respectively. There was no toxicity at 1.0 0 and 1 - 5 g F.u./m2/day. At 2 g F.u./m2/day, one patient with gastric carcinoma (post-gastrectomy) previously treated with F.u., doxorubicin, and carmustine (B.c.N.u.) became leukopenic and had severe mucositis (ulcers, unable to eat). At 2.25 g F.u./m2/day one patient had severe myelosuppression and severe mucositis, and died of septicaemia. This patient had bulky abdominal metastases from ovarian carcinoma resistant to chlorambucil and cis-platinum treatment, and she had great difficulty taking the allopurinol by mouth because of nausea and vomiting. Three other patients had mild mucositis (sore mouth, no ulcers) without myelosuppression. One patient received 2.5 g F.u./m2 with mild mucositis without myelosuppression. A further patient received 2-9 F.u./m2/day and had myelosuppression complicated by -non-fatal septicEsmia. He had tolerated 2.25 g F. u./m2/day without toxicity. At doses at or below 1.5g/m2/day there were no objective
5-day continuous
F.u./m2/day), and
1 2 3
Moertel, C. G. New Engl. J. Med. 1978, 299,
1049.
Moertel,C G. and Reitemeier, R J. Surg. Clins N. Am 1967, 47, 929. Seifert, P., Baker, L. H., Reed, M L., Vaitkevicius, V. K. Cancer, 1975, 36, 123.
4
Fox, R M., Wood, M H , O’Sullivan, W. J. J clin. Invest. 1971, 50, 1050. 5. Gallo, R C., Perry, S., Breitman, T. R Biochem. Pharmac 1968, 17, 2185. 6 Schwarts, P. M., Handschumacher, R E. Proc Am Ass. Cancer Res. 1978, 111
R. M. Fox R. L. WOODS M. H. N. TATTERSALL
G. M. BRODIE
ZINC CITRATE, HUMAN MILK, AND ACRODERMATITIS ENTEROPATHICA
SIR,-Acrodermatitis enteropathica (A.E.), a genetic disease characterised by severe dermatitis, diarrhoea, and alopecia, is a disorder of zinc metabolism,I,2 including abnormal zinc absorption.3,’ For over thirty years, however, human milk has been known to be therapeutic for the disease.5 Recent work from this laboratory indicated that, in human milk, zinc was carried in part by a low-molecular-weight zinc-binding ligand (z.B.L.) found in only very small amounts in cow’s milk,6 and the hypothesis was developed that this z.B.L. was important for intestinal absorption of zinc in the normal neonate as well as in A.E. patients.’ Further work showed that z.B.L. from both human and rat milk enhanced zinc absorption in the neonatal rat.8 We have now purified, isolated, and identified the z.B.L. from human milk. Defatted samples of human milk were subjected to gel filtration on columns treated with sodium borohydride to reduce charged groups. Zinc recovery from such columns varied from 98to 102%, even with as little as 0-11 ug zinc in the sample (unpublished). Purification of the z.B.L.-Zn complex was accomplished by ultrafiltration in an Amicon cell followed by anion-exchange chromatography on a ’DEAESephadex’ column. The z.B.L. was identified by infrared and huclear-magneticresonance spectroscopy as citrate, and confirmed by enzymatic assay.9 The citrate peak coincided with the Zn peak in all runs of gel filtration and ion-exchange chromatography. In addition, synthetic zinc citrate behaved chromatographically like the Z.B.L.-Zn complex. Similar work with cow’s milk showed that citrate was also present in these samples, but the amount of zinc complexed to citrate was very small, only a quarter that in human milk. It is probable that the high-molecular-weight compound to which Zn is mainly bound in cow’s milk is casein, present in bovine milk at about 10 times its concentration in human milk.’" Zn bound to case casein may therefore be unavailable to the young infant with its problems of casein digestion. Thus, the relatively high amount of citrate-bound Zn in human milk may be responsible for its therapeutic value in 1. 2. 3.
Moynahan, E. J., Barnes, P. M. Lancet, 1973, i, 676. Neldner, K. H., Hambidge, K. M. New Engl J. Med. 1975, 292, 879. Lombeck, I., Schnippering, H. G., Kasperek, K., Ritzl, F., Kastner, H., Feinendegen, L. E., Bremer, H. J. Z. Kinderheilk 1975, 120, 181. 4. Jackson, M. J. J. clin. Path. 1977, 30, 284. 5. Brandt, T. Acta derm. vener. Stockh. 1937, 17, 513. 6 Eckhert, C. D., Sloan, M. V., Duncan, J. R., Hurley, L. S. Science, 1977, 195, 789. 7. Hurley, L. S , Duncan, J R., Sloan, M. V., Eckhert, C. D. Proc. natn Acad Sci. U.S.A 1977, 74, 3457. 8. Duncan, J. R., Hurley, L. S. Am. J. Physiol. 1978, 235, E556. 9. Lönnerdal, B., Stanislowski, A. G., Hurley, L. S. Fedn Proc. (in the press). 10 Fomon, S. J. Infant Nutrition. Philadelphia, 1974.
678 A.E., and may enhance absorption of this essential ment in normal human neonates.
trace
ele-
Department of Nutrition, Agricultural Experimental Station,
College of Agricultural and Environmental Sciences, Sciences,
University of California, Davis, California 95616, U.S.A.
LUCILLE S. HURLEY BO LÖNNERDAL ANNA G. STANISLOWSKI
POLYARTERITIS NODOSA AND HAIRY-CELL LEUKÆMIA
SIR,-Classic polyarteritis nodosa is
a systemic necrotising affecting medium and small muscular arteries. The aetiology is usually unknown, though some cases seem to be related to hepatitis-B-virus infection.’ The host factors which allow virus-antibody complexes to persist in the circulation and deposit in vessel wallsl,2 are poorly defined. The occurrence of vasculitis in patients with chronic lymphoproliferative neoplasms3 such as chronic lymphatic leukaemia, Hodgkin’s disease, and multiple myeloma may provide insight into this problem since immunological abnormalities and recurrent infections are common to all. Patients with hairy-cell leukaemia are very susceptible to infection4’ and are reported to have serum factors which impair monocyte function.6 For this reason, we believe that the coincidence of hairy-cell leuksemia and polyarteritis nodosa in the patient described in this report may have pathogenetic implications. A 36-year-old man presented with an indolent septic ulcer on the right index finger in April, 1976. He was pale and had moderate splenomegaly. He had pancytopenia with typical hairy-cells accounting for 4% of the total white-cell count. Splenectomy was done in July, 1976, after which he had bacterial pneumonia and herpes labialis. Several minor skin and oropharyngeal infections occurred after discharge from hospi-
vasculitis
2 months the patient had severe rest pain. He was admitted to hospital where he was noted to be normotensive with weak pulsations in the right dorsalis pedis and posterior tibial arteries. The ankle-occlusion pressure was 140 mm Hg on the left and 95 mm Hg on the right. The rest of the physical examination was normal apart from mild axillary and inguinal lympha-
denopathy. The Hb was 10.8 g/dl, w.B.c. 4x 109/1 (4% hairy-cells), and platelets 400x 109/1. Bone-marrow and lymph-node histology revealed extensive hairy-cell infiltration. Renal and liver function tests were normal and neither HBs antigen nor antibody were detected. Serum-IgG was raised at 38.0 g/1 but tests for rheumatoid factor, antinuclear antibody, and cryoglobulins were negative. Total serum complement (CHsa) and the early complement components were low, suggesting activation of the classical pathway. Circulating immune complexes were detected (Clq binding assay). Arteriography showed numerous microaneurysms 2-5 mm in diameter in the inferior mesenteric circulation and in the arteries of both legs (see figure). Since both polyarteritis nodosa and hairy-cell leukaemia are a chance association is highly unlikely. The susceptibility of patients with hairy-cell leuksemia to infection is largely due to neutropenia, but may also result from a profound monocytopenia and impaired monocyte function.4 The monocyte-macrophage system has a central role in the clearance of immune complexes, and any factor interfering with function of this system could result in the prolonged circulation and deposition of these complexes. Although current reviews’5 do not comment on the occurrence of vasculitic disorders in hairy-cell leukaemia, the frequent use of corticosteroids and immunosuppressive drugs may modify the nature and expression of a concurrent vasculitis. We believe this to be the first report of an association between the two conditions. More detailed studies of other patients with hairy-cell leukaemia are in progress.
rare,
tal. 1977 the patient had several episodes of arthritis of both knees which responded to short courses of prednisone. In March, 1978, intermittent claudication of the right leg developed. The claudication distance rapidly decreased and within
During
Gocke, D. J., Hsu, K., Morgan, C., Bombardieri, S., Lockshin, M., Christian, C. L. Lancet, 1970, ii, 1149. 2. Gerber, M. A., Brodin, A., Steinberg, D., Vernance, S., Yang, C. H., Paronetto, F. New Engl. J. Med. 1972, 286, 14. 3. Fauci, A. S., Haynes, B. F., Katz, P. Ann intern. Med. 1978, 89, 660 4 Golomb, H. M., Catovsky, D., Golde, D.W. ibid. 1978, 89, 677. 5. Turner, A., Kjeldsberg, C. R. Medicine, 1978, 57, 478. 6. Kjeldsberg, C. R. Ann, intern Med. 1978, 88, 268.
Royal Postgraduate Medical School, London W12
G. R. V. HUGHES K. B. ELKON R. SPILLER D. CATOVSKY
I. JAMIESON
1.
YERSINIA ENTEROCOLITICA AND THYROID DISEASES IN SPAIN
SIR,-Studies in Denmark’2 and the U.S.A.3 have revealed high incidence of anti Yersinia enterocolitica (Y.E.) antibodies in several thyroid diseases. In Denmark, the prevalence of a
anti-Y.E. antibodies in the normal population is higher than it is in U.S.A.; nevertheless the incidence of antibodies to Y.E. serotype 3 is similar in patients of both countries with thyroid diseases. We have looked for anti-Y.E. antibodies serotypes 3 and 9, in sera of 154 patients with a variety of thyroid diseases and in 44 controls. Agglutination was done in a microtitre system
(Dynatech Corporation, Cambridge, Massachusetts) using as antigen strains supplied by Dr Sten Winblad (Lund University, Mahno, Sweden). In positive cases, seroagglutination to brucella was tested by the same method to see if there was a crossreaction. Titres of 1/8 or greater were considered significant (see table). The frequency of anti-Y.E. antibodies was similar in control individuals and in patients with thyroid diseases; positive cases were serotype 9 except in 1 control and in 1 patient with multinodular goitre. In positive cases with Graves’ disease, there was no relation to functional status; none of the positive cases 1. 2.
...
Microaneurysms
in arteries of both
legs.
Bech, K., Larsen, J. H., Hansen, J. M. Lancet, 1974, ii, 951. Bech, K., Nerup, J., Larsen, J. H. Acta endocr. 1977, 84, 87. 3. Shenkman, L., Bottone, E. J. Ann. intern. Med. 1976, 85, 735.
G. PASTORE P. DENTICO R. BUONGIORNO G. ANGARANO O. SCHIRALDI
Infectious Diseases Clinic, Department of Clinical Immunology, and II Medical Clinic,
responses. However, at F.u. doses 2.00 g/ml/day there five objective tumour regressions in the ten patients treated. Four responding patients had colorectal carcinoma, and one had gastric carcinoma. We believe that allopurinol may modulate F.u. toxicity in man, allowing a two-fold increase in dose. Tumour response does not seem to be prevented by concurrent administration of allopurinol. We are now investigating the use of intravenous allopurinol and the biochemical mechanisms of allopurinol modulation of the F.u. response in man. tumour were
Ludwig Institute for Cancer Research, University of Sydney, Sydney, New South Wales 2006, Australia
A. TURSI
University of Bari Medical School, 70124 Bari, Italy
M. P. LORIA
Department of Medical Oncology, Prince Henry’s Hospital, Melbourne, Victoria
ALLOPURINOL MODULATION OF HIGH-DOSE FLUOROURACIL TOXICITY
SIR,-Fluorouracil (F.u.) causes temporary tumour regression in approximately 150 of patients with advanced gastrointestinal cancer. Several schedules of drug administration have been used with no clear advantage having been demonstrated.’ However, responses are more common in patients who have drug toxicity, suggesting a steep dose-response curve.2 The maximum tolerated daily dose of F.U. given by infusion has been 30mg/kg/day (1-1-1-2g g at 35 mg F.u./kg/day, seven out of eight patients had severe stomatitis.3 Oxypurinol, the in-vivo active metabolite of allopurinol, is a strong inhibitor of orotate phosphoribosyltransferase4 and a weak inhibitor of thymidine phosphorylase,5 two of the three enzymes which activate F.u. The toxicity of F.u. in mice is reduced by concurrent allopurinol administration, presumably because pathways activating F.u. in normal tissue are blocked.6 We have used F.u. infusions and concurrent allopurinol in thirteen patients with advanced cancer (colorectal in ten cases, ovanan in one, gastric in one, prostatic in one). Patients received allopurinol, 300 mg three times a day by mouth on days 1-6 with 2 litres of normal saline i.v. daily. F.u. was given, as a 24 h i.v. infusion on days 2-6 in the saline. The first three patients received 1 g F.u./m2/day x 5 and doses were then increased in these patients, and in new patients, to 1-5, 2.0, 225, 2.5, and 2.9 g F.u./m day x 5; the number of patients treated at these dose levels were three, three, eight, one, and one, respectively. There was no toxicity at 1.0 0 and 1 - 5 g F.u./m2/day. At 2 g F.u./m2/day, one patient with gastric carcinoma (post-gastrectomy) previously treated with F.u., doxorubicin, and carmustine (B.c.N.u.) became leukopenic and had severe mucositis (ulcers, unable to eat). At 2.25 g F.u./m2/day one patient had severe myelosuppression and severe mucositis, and died of septicaemia. This patient had bulky abdominal metastases from ovarian carcinoma resistant to chlorambucil and cis-platinum treatment, and she had great difficulty taking the allopurinol by mouth because of nausea and vomiting. Three other patients had mild mucositis (sore mouth, no ulcers) without myelosuppression. One patient received 2.5 g F.u./m2 with mild mucositis without myelosuppression. A further patient received 2-9 F.u./m2/day and had myelosuppression complicated by -non-fatal septicEsmia. He had tolerated 2.25 g F. u./m2/day without toxicity. At doses at or below 1.5g/m2/day there were no objective
5-day continuous
F.u./m2/day), and
1 2 3
Moertel, C. G. New Engl. J. Med. 1978, 299,
1049.
Moertel,C G. and Reitemeier, R J. Surg. Clins N. Am 1967, 47, 929. Seifert, P., Baker, L. H., Reed, M L., Vaitkevicius, V. K. Cancer, 1975, 36, 123.
4
Fox, R M., Wood, M H , O’Sullivan, W. J. J clin. Invest. 1971, 50, 1050. 5. Gallo, R C., Perry, S., Breitman, T. R Biochem. Pharmac 1968, 17, 2185. 6 Schwarts, P. M., Handschumacher, R E. Proc Am Ass. Cancer Res. 1978, 111
R. M. Fox R. L. WOODS M. H. N. TATTERSALL
G. M. BRODIE
ZINC CITRATE, HUMAN MILK, AND ACRODERMATITIS ENTEROPATHICA
SIR,-Acrodermatitis enteropathica (A.E.), a genetic disease characterised by severe dermatitis, diarrhoea, and alopecia, is a disorder of zinc metabolism,I,2 including abnormal zinc absorption.3,’ For over thirty years, however, human milk has been known to be therapeutic for the disease.5 Recent work from this laboratory indicated that, in human milk, zinc was carried in part by a low-molecular-weight zinc-binding ligand (z.B.L.) found in only very small amounts in cow’s milk,6 and the hypothesis was developed that this z.B.L. was important for intestinal absorption of zinc in the normal neonate as well as in A.E. patients.’ Further work showed that z.B.L. from both human and rat milk enhanced zinc absorption in the neonatal rat.8 We have now purified, isolated, and identified the z.B.L. from human milk. Defatted samples of human milk were subjected to gel filtration on columns treated with sodium borohydride to reduce charged groups. Zinc recovery from such columns varied from 98to 102%, even with as little as 0-11 ug zinc in the sample (unpublished). Purification of the z.B.L.-Zn complex was accomplished by ultrafiltration in an Amicon cell followed by anion-exchange chromatography on a ’DEAESephadex’ column. The z.B.L. was identified by infrared and huclear-magneticresonance spectroscopy as citrate, and confirmed by enzymatic assay.9 The citrate peak coincided with the Zn peak in all runs of gel filtration and ion-exchange chromatography. In addition, synthetic zinc citrate behaved chromatographically like the Z.B.L.-Zn complex. Similar work with cow’s milk showed that citrate was also present in these samples, but the amount of zinc complexed to citrate was very small, only a quarter that in human milk. It is probable that the high-molecular-weight compound to which Zn is mainly bound in cow’s milk is casein, present in bovine milk at about 10 times its concentration in human milk.’" Zn bound to case casein may therefore be unavailable to the young infant with its problems of casein digestion. Thus, the relatively high amount of citrate-bound Zn in human milk may be responsible for its therapeutic value in 1. 2. 3.
Moynahan, E. J., Barnes, P. M. Lancet, 1973, i, 676. Neldner, K. H., Hambidge, K. M. New Engl J. Med. 1975, 292, 879. Lombeck, I., Schnippering, H. G., Kasperek, K., Ritzl, F., Kastner, H., Feinendegen, L. E., Bremer, H. J. Z. Kinderheilk 1975, 120, 181. 4. Jackson, M. J. J. clin. Path. 1977, 30, 284. 5. Brandt, T. Acta derm. vener. Stockh. 1937, 17, 513. 6 Eckhert, C. D., Sloan, M. V., Duncan, J. R., Hurley, L. S. Science, 1977, 195, 789. 7. Hurley, L. S , Duncan, J R., Sloan, M. V., Eckhert, C. D. Proc. natn Acad Sci. U.S.A 1977, 74, 3457. 8. Duncan, J. R., Hurley, L. S. Am. J. Physiol. 1978, 235, E556. 9. Lönnerdal, B., Stanislowski, A. G., Hurley, L. S. Fedn Proc. (in the press). 10 Fomon, S. J. Infant Nutrition. Philadelphia, 1974.
678 A.E., and may enhance absorption of this essential ment in normal human neonates.
trace
ele-
Department of Nutrition, Agricultural Experimental Station,
College of Agricultural and Environmental Sciences, Sciences,
University of California, Davis, California 95616, U.S.A.
LUCILLE S. HURLEY BO LÖNNERDAL ANNA G. STANISLOWSKI
POLYARTERITIS NODOSA AND HAIRY-CELL LEUKÆMIA
SIR,-Classic polyarteritis nodosa is
a systemic necrotising affecting medium and small muscular arteries. The aetiology is usually unknown, though some cases seem to be related to hepatitis-B-virus infection.’ The host factors which allow virus-antibody complexes to persist in the circulation and deposit in vessel wallsl,2 are poorly defined. The occurrence of vasculitis in patients with chronic lymphoproliferative neoplasms3 such as chronic lymphatic leukaemia, Hodgkin’s disease, and multiple myeloma may provide insight into this problem since immunological abnormalities and recurrent infections are common to all. Patients with hairy-cell leukaemia are very susceptible to infection4’ and are reported to have serum factors which impair monocyte function.6 For this reason, we believe that the coincidence of hairy-cell leuksemia and polyarteritis nodosa in the patient described in this report may have pathogenetic implications. A 36-year-old man presented with an indolent septic ulcer on the right index finger in April, 1976. He was pale and had moderate splenomegaly. He had pancytopenia with typical hairy-cells accounting for 4% of the total white-cell count. Splenectomy was done in July, 1976, after which he had bacterial pneumonia and herpes labialis. Several minor skin and oropharyngeal infections occurred after discharge from hospi-
vasculitis
2 months the patient had severe rest pain. He was admitted to hospital where he was noted to be normotensive with weak pulsations in the right dorsalis pedis and posterior tibial arteries. The ankle-occlusion pressure was 140 mm Hg on the left and 95 mm Hg on the right. The rest of the physical examination was normal apart from mild axillary and inguinal lympha-
denopathy. The Hb was 10.8 g/dl, w.B.c. 4x 109/1 (4% hairy-cells), and platelets 400x 109/1. Bone-marrow and lymph-node histology revealed extensive hairy-cell infiltration. Renal and liver function tests were normal and neither HBs antigen nor antibody were detected. Serum-IgG was raised at 38.0 g/1 but tests for rheumatoid factor, antinuclear antibody, and cryoglobulins were negative. Total serum complement (CHsa) and the early complement components were low, suggesting activation of the classical pathway. Circulating immune complexes were detected (Clq binding assay). Arteriography showed numerous microaneurysms 2-5 mm in diameter in the inferior mesenteric circulation and in the arteries of both legs (see figure). Since both polyarteritis nodosa and hairy-cell leukaemia are a chance association is highly unlikely. The susceptibility of patients with hairy-cell leuksemia to infection is largely due to neutropenia, but may also result from a profound monocytopenia and impaired monocyte function.4 The monocyte-macrophage system has a central role in the clearance of immune complexes, and any factor interfering with function of this system could result in the prolonged circulation and deposition of these complexes. Although current reviews’5 do not comment on the occurrence of vasculitic disorders in hairy-cell leukaemia, the frequent use of corticosteroids and immunosuppressive drugs may modify the nature and expression of a concurrent vasculitis. We believe this to be the first report of an association between the two conditions. More detailed studies of other patients with hairy-cell leukaemia are in progress.
rare,
tal. 1977 the patient had several episodes of arthritis of both knees which responded to short courses of prednisone. In March, 1978, intermittent claudication of the right leg developed. The claudication distance rapidly decreased and within
During
Gocke, D. J., Hsu, K., Morgan, C., Bombardieri, S., Lockshin, M., Christian, C. L. Lancet, 1970, ii, 1149. 2. Gerber, M. A., Brodin, A., Steinberg, D., Vernance, S., Yang, C. H., Paronetto, F. New Engl. J. Med. 1972, 286, 14. 3. Fauci, A. S., Haynes, B. F., Katz, P. Ann intern. Med. 1978, 89, 660 4 Golomb, H. M., Catovsky, D., Golde, D.W. ibid. 1978, 89, 677. 5. Turner, A., Kjeldsberg, C. R. Medicine, 1978, 57, 478. 6. Kjeldsberg, C. R. Ann, intern Med. 1978, 88, 268.
Royal Postgraduate Medical School, London W12
G. R. V. HUGHES K. B. ELKON R. SPILLER D. CATOVSKY
I. JAMIESON
1.
YERSINIA ENTEROCOLITICA AND THYROID DISEASES IN SPAIN
SIR,-Studies in Denmark’2 and the U.S.A.3 have revealed high incidence of anti Yersinia enterocolitica (Y.E.) antibodies in several thyroid diseases. In Denmark, the prevalence of a
anti-Y.E. antibodies in the normal population is higher than it is in U.S.A.; nevertheless the incidence of antibodies to Y.E. serotype 3 is similar in patients of both countries with thyroid diseases. We have looked for anti-Y.E. antibodies serotypes 3 and 9, in sera of 154 patients with a variety of thyroid diseases and in 44 controls. Agglutination was done in a microtitre system
(Dynatech Corporation, Cambridge, Massachusetts) using as antigen strains supplied by Dr Sten Winblad (Lund University, Mahno, Sweden). In positive cases, seroagglutination to brucella was tested by the same method to see if there was a crossreaction. Titres of 1/8 or greater were considered significant (see table). The frequency of anti-Y.E. antibodies was similar in control individuals and in patients with thyroid diseases; positive cases were serotype 9 except in 1 control and in 1 patient with multinodular goitre. In positive cases with Graves’ disease, there was no relation to functional status; none of the positive cases 1. 2.
...
Microaneurysms
in arteries of both
legs.
Bech, K., Larsen, J. H., Hansen, J. M. Lancet, 1974, ii, 951. Bech, K., Nerup, J., Larsen, J. H. Acta endocr. 1977, 84, 87. 3. Shenkman, L., Bottone, E. J. Ann. intern. Med. 1976, 85, 735.
