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SERUM-COMPLEMENT LEVELS IN HÆMOLYTIC-URÆMIC SYNDROME
294
agranulocytosis (more than 200 neutrophils per c.mm., moderate signs of infection) were given antibiotics active against gram-negative enterobacteria (cephalosporine plus streptomycin), y-globulin, and prednisolone (30-90 mg. per day). In 3 severe cases (fewer neutrophils, signs of severe infection), granulocyte transfusions were also given. Only 1 patient died of agranulocytosis in the overt stage. Another patient, an 86-year-old man, died of intercurrent disease (generalised arteriosclerosis) a few months after being discharged; he had slight residual leucopenia and thrombocytopenia. Those with moderate
If a percentage mortality were calculated on a group as small as the present one, it would be only 7%. A standardised programme such as that described may improve the prognosis in agranulocytosis. Hæmatology Section, Karolinska Hospital, PETER REIZENSTEIN Stockholm 60, KARIN EDGARDH. Sweden.
SERUM-COMPLEMENT LEVELS IN HÆMOLYTIC-URÆMIC SYNDROME SIR,-In both the haemolytic-uraemic syndrome (H.U.S.) and thrombotic thrombocytopenic purpura, Cameron and Vick1 noted a low C3 concentration in 5 out of 10 patients during the acute phase of the disease. Kaplan et al.2 found initial low Cs levels in 3 out of 10 patients with H.U.S.
In 33 children with H.u.s. the 1. 2.
C3 level
was
measured in
Cameron, J. S., Vick, R. Lancet, 1973, ii, 975. Kaplan, B. S., Thomson, P. D., Macnab, G. M. ibid.
p. 1505.
SERUM-COMPLEMENT LEVELS IN HE.MOLYTIC-URE.MIC SYNDROME I
I
I
I
I
I
the acute phase by radial immunodiffusion. C4 and proactivator-activator were measured by the same technique in 18 children. The initial C, values were below normal in 10 out of 21 patients with anuria, in 2 out of 8 patients with oliguria, and in 2 out of 4 patients with a normal diuresis (see accompanying table). In most of the cases only a slight decrease was noted. In only 2 out of 18 children a decrease of C4 levels and in only 1 out of 18 children a decrease of proactivator-activator was shown. There is no evidence that either the classical or the alternative pathway is involved in the fall of C3. The suggestion of Cameron and Vick that the fall in C, is brought about by the action of plasmin seems improbable. In patients treated with urokinase which activates their plasminogen to plasmin, the serum-Ca levels are unaffected by fibrinolytic therapy. We have to study the synthesis and catabolism of Cg in patients with H.U.S. In renal histological specimens no Cs deposition by immunofluorescent methods could be shown. 4-6 L. MONNENS G. HENDRICKX Department of Pædiatrics, VAN WIERINGEN P. University of Nijmegen, P. VAN MUNSTER. The Netherlands.
IMPAIRED NEUTROPHIL PHAGOCYTOSIS
SIR,-Lately, two girls, aged 6 years (case 1) and 4t years (case 2), who had a syndrome similar to that described by Buckley et al.,’ were referred to us. Both had multiple recurrent cold staphylococcal abscesses, extensive mycotic and bacterial skin infections, chronic bronchial infections, very high IgE levels ( > 3500 u per ml.), and slight eosinophilia. Lymphoblast transformation was normal after phytohaemagglutinin stimulation but not after Candida albicans extract stimulation. Total hasmolytic complement, Cs, C4, IgM, IgG, IgA, N.B.T. dye reduction, and immunocytoadherence (rosette) were within normal range. The myeloperoxidase test was also normal. Diphtheria, typhoid, and tetanus antibodies were low or absent after vaccination. In autologous serum the phagocytosis of yeasts by neutrophils in case 2 was impaired; it was restored by addition of AB serum. Delayed hypersensitivity reactions to D.N.C.B. were absent in both girls; reactions to candidin were absent in case 1 and poor in case 2. In case 1 we gave levamisole, a drug which restores deficient
depressed host defence mechanisms11 by activating phagocytosis 9 (e.g., of colloidal carbon particles 10 and of lipid emulsions 11). She was given 2-5 mg. per kg. of levamisole orally on three consecutive days every two weeks. After one month of treptment (i.e., six doses of levamisole) abscesses and skin and bronchial infections completely disappeared. High delayed hypersensitivity developed to various dilutions of the skin antigens. Lymphoblast transformation after stimulation by C. albicans extract became normal. IgE levels, however, remained high. After two years’ treatment with three oral doses of levamisole every two weeks, symptoms have not recurred. All laboratory tests have remained normal, but IgE is still high. Phagocytosis
or
3.
Tomar, R. H., Kolchins, D. Thrombos. Diathes. hæmorrh. 1972, 37,
4.
Habib, R., Courtecuisse, V., Leclerc, F., Mathieu, H., Royer, P. Archs fr. Pédiat. 1969, 26, 391. Gervais, M., Richardson, J. B., Drummond, K. N. Pediatrics, Springfield, 1971, 47, 352. Franklin, W. A., Simon, N. M., Potter, E. W., Krumlovsky, F. A. Archs Path. 1972, 94, 230. Buckley, R. H., Wray, B. B., Belmaker, E. Z. Pediatrics, Springfield. 1972, 49, 59. Brugmans, J., Schuermans, V., De Cock, W., Thienpont, D., Janssen, P., Verhaegen, H., Van Nimmen, L., Louwagie, A. C., Stevens, E. Life Sci. 1973, 13, 1499. Verhaegen, H., De Cree, J., Verbruggen, F., Hoebeke, J., De Brabander, M., Brugmans, J. Verh. d. Ges. inn. Med. 1973, 79, 623 Hoebeke, J., Franchi, G. J. Reticuloend. Soc. 1973, 14, 317. Verhaegen, H., De Cree, J., De Cock, W., Verbruggen, F. New Engl. J. Med. 1973, 229, 1148.
389.
5.
6. 7. 8. ’
c.: normal range 77-142 mg. per 100 ml. C,: normal range 15-45 mg. per 100 ml. Proactivator-activator: normal range 14-26 mg. per 100 ml. ml. per sq. m. per 24 hours. O=oliguria<200 A=anuria < 10 ml. per 24 hours. N =normal diuresis.
9.
10. 11.
agranulocytosis (more than 200 neutrophils per c.mm., moderate signs of infection) were given antibiotics active against gram-negative enterobacteria (cephalosporine plus streptomycin), y-globulin, and prednisolone (30-90 mg. per day). In 3 severe cases (fewer neutrophils, signs of severe infection), granulocyte transfusions were also given. Only 1 patient died of agranulocytosis in the overt stage. Another patient, an 86-year-old man, died of intercurrent disease (generalised arteriosclerosis) a few months after being discharged; he had slight residual leucopenia and thrombocytopenia. Those with moderate
If a percentage mortality were calculated on a group as small as the present one, it would be only 7%. A standardised programme such as that described may improve the prognosis in agranulocytosis. Hæmatology Section, Karolinska Hospital, PETER REIZENSTEIN Stockholm 60, KARIN EDGARDH. Sweden.
SERUM-COMPLEMENT LEVELS IN HÆMOLYTIC-URÆMIC SYNDROME SIR,-In both the haemolytic-uraemic syndrome (H.U.S.) and thrombotic thrombocytopenic purpura, Cameron and Vick1 noted a low C3 concentration in 5 out of 10 patients during the acute phase of the disease. Kaplan et al.2 found initial low Cs levels in 3 out of 10 patients with H.U.S.
In 33 children with H.u.s. the 1. 2.
C3 level
was
measured in
Cameron, J. S., Vick, R. Lancet, 1973, ii, 975. Kaplan, B. S., Thomson, P. D., Macnab, G. M. ibid.
p. 1505.
SERUM-COMPLEMENT LEVELS IN HE.MOLYTIC-URE.MIC SYNDROME I
I
I
I
I
I
the acute phase by radial immunodiffusion. C4 and proactivator-activator were measured by the same technique in 18 children. The initial C, values were below normal in 10 out of 21 patients with anuria, in 2 out of 8 patients with oliguria, and in 2 out of 4 patients with a normal diuresis (see accompanying table). In most of the cases only a slight decrease was noted. In only 2 out of 18 children a decrease of C4 levels and in only 1 out of 18 children a decrease of proactivator-activator was shown. There is no evidence that either the classical or the alternative pathway is involved in the fall of C3. The suggestion of Cameron and Vick that the fall in C, is brought about by the action of plasmin seems improbable. In patients treated with urokinase which activates their plasminogen to plasmin, the serum-Ca levels are unaffected by fibrinolytic therapy. We have to study the synthesis and catabolism of Cg in patients with H.U.S. In renal histological specimens no Cs deposition by immunofluorescent methods could be shown. 4-6 L. MONNENS G. HENDRICKX Department of Pædiatrics, VAN WIERINGEN P. University of Nijmegen, P. VAN MUNSTER. The Netherlands.
IMPAIRED NEUTROPHIL PHAGOCYTOSIS
SIR,-Lately, two girls, aged 6 years (case 1) and 4t years (case 2), who had a syndrome similar to that described by Buckley et al.,’ were referred to us. Both had multiple recurrent cold staphylococcal abscesses, extensive mycotic and bacterial skin infections, chronic bronchial infections, very high IgE levels ( > 3500 u per ml.), and slight eosinophilia. Lymphoblast transformation was normal after phytohaemagglutinin stimulation but not after Candida albicans extract stimulation. Total hasmolytic complement, Cs, C4, IgM, IgG, IgA, N.B.T. dye reduction, and immunocytoadherence (rosette) were within normal range. The myeloperoxidase test was also normal. Diphtheria, typhoid, and tetanus antibodies were low or absent after vaccination. In autologous serum the phagocytosis of yeasts by neutrophils in case 2 was impaired; it was restored by addition of AB serum. Delayed hypersensitivity reactions to D.N.C.B. were absent in both girls; reactions to candidin were absent in case 1 and poor in case 2. In case 1 we gave levamisole, a drug which restores deficient
depressed host defence mechanisms11 by activating phagocytosis 9 (e.g., of colloidal carbon particles 10 and of lipid emulsions 11). She was given 2-5 mg. per kg. of levamisole orally on three consecutive days every two weeks. After one month of treptment (i.e., six doses of levamisole) abscesses and skin and bronchial infections completely disappeared. High delayed hypersensitivity developed to various dilutions of the skin antigens. Lymphoblast transformation after stimulation by C. albicans extract became normal. IgE levels, however, remained high. After two years’ treatment with three oral doses of levamisole every two weeks, symptoms have not recurred. All laboratory tests have remained normal, but IgE is still high. Phagocytosis
or
3.
Tomar, R. H., Kolchins, D. Thrombos. Diathes. hæmorrh. 1972, 37,
4.
Habib, R., Courtecuisse, V., Leclerc, F., Mathieu, H., Royer, P. Archs fr. Pédiat. 1969, 26, 391. Gervais, M., Richardson, J. B., Drummond, K. N. Pediatrics, Springfield, 1971, 47, 352. Franklin, W. A., Simon, N. M., Potter, E. W., Krumlovsky, F. A. Archs Path. 1972, 94, 230. Buckley, R. H., Wray, B. B., Belmaker, E. Z. Pediatrics, Springfield. 1972, 49, 59. Brugmans, J., Schuermans, V., De Cock, W., Thienpont, D., Janssen, P., Verhaegen, H., Van Nimmen, L., Louwagie, A. C., Stevens, E. Life Sci. 1973, 13, 1499. Verhaegen, H., De Cree, J., Verbruggen, F., Hoebeke, J., De Brabander, M., Brugmans, J. Verh. d. Ges. inn. Med. 1973, 79, 623 Hoebeke, J., Franchi, G. J. Reticuloend. Soc. 1973, 14, 317. Verhaegen, H., De Cree, J., De Cock, W., Verbruggen, F. New Engl. J. Med. 1973, 229, 1148.
389.
5.
6. 7. 8. ’
c.: normal range 77-142 mg. per 100 ml. C,: normal range 15-45 mg. per 100 ml. Proactivator-activator: normal range 14-26 mg. per 100 ml. ml. per sq. m. per 24 hours. O=oliguria<200 A=anuria < 10 ml. per 24 hours. N =normal diuresis.
9.
10. 11.