1318 average sodium concentration of 75 mmol/1 (range For the sugar, the amount which can be held levelled in four bent fingers, the sugar not to cover the palm, gave an average of 18.3(range 15.8-23-0). These averages are similar to those obtained with the measuring spoons, although the ranges are wider. an
51-105).
Basic Sciences Laboratory and M.C.H. Division of Preventive Medicine,
Section,
Ministry of Health, Maputo, Mozambique
ANGELA MELAMED MALCOLM SEGALL
HUMAN TOXOCARA INFECTION IN WEST OF SCOTLAND
PRIST should be used for confirmation of the diagnosis and for the monitoring of antibody levels in relation to duration of infection and antibody response to treatment. We feel that our findings indicate a high prevalence of Toxocara infection and point to the need for more widespread scrutiny of the population so that the true pathological significance of the detection of Toxocara antibodies can be assessed.
Department of Bacteriology, Stobhill General Hospital, Glasgow G21 3UW
R. W. A. GIRDWOOD
Department of Zoology, University of Glasgow
H. V. SMITH R. G. BRUCE R. QUINN
Six,-The pathogenic propensity of Toxocara canis larva: for
first demonstrated in 1952,1 and the public-health of importance Toxocara infection in the U.K. has been extensively reviewed by Woodruff.2-4 T. canis is a common parasite of dogs, and infected dogs excrete large numbers of potentially infective ova into the environment.56However, the prevalence of human infection and, more importantly, the human disease attributable to the parasite remain controversial. The "dog problem" has lately received publicity in the Press and on television in the U.K., and some district councils are setting up schemes for the collection of stray animals. We report here the preliminary findings of a survey of the prevalance of human Toxocara infection in the West of Scotland. Diagnosis of toxocariasis is, with few exceptions, dependent on the demonstration of antibodies to the parasite or its products in the serum of suspected cases. Most surveys of human infection have been based on tests with somatic antigens derived from adult or larval worms.’·8 However, such somatic antigens lack sensitivity and show a high degree of cross-reactivity with Ascaris.9 The development of an in-vitro system for the maintenance of second-stage larvx’O has permitted the harvesting of larval secretions for use as a diagnostic antigen. In the rabbit we have found such a secretory antigen preparation to be both sensitive and specific; there were no cross-reactions between experimentally induced visceral larva migrans of T. canis, Toxascaris leionina, A. lumbricoides and A. suum oriman was
gins. Using counterimmunoelectrophoresis (C.LE.), indirect fluorescent antibody tests (LF.A.), and the paper radioimmunosorbent test (PRIST) we obtained the following results with serea from patients and blood-donors in the West of Scotland:
*
Only 2 of the
13 positive sera were of West of Scotland origin. 1 schistosome, 1 Fasciola, 1
t 4 Ascaris, 3 hookworm, 4 EnterobIUs, Filaria, and 2 Taenia.
with the three tests suggests that the c.i.E. and suitable for rapid screening procedures and that
Experience l.F.A.
are
Beaver, P. C., Snyder, C. H., Carrera, G. M., Dent, J. H., Lafferty, J. W Pediatrics, 1952, 9, 7. 2. Woodruff, A. W. Br. med. J. 1970, iii, 663. 3. Woodruff, A. W. Br. vet. J. 1975, 131, 627. 4. Woodruff, A. W. Envir. Hlth, 1976, 1, 29. 5. Girdwood, R. W. A., Quinn, R., Smith, H. V., Bruce, R. G., Trans. R. Soc. trop. Med. Hyg. 1976, 70, 284. 6. Jacobs, D. E., Pegg, E. J., Stevenson, P. J. Small Anim. Pract 1977, 18, 79. 7. Bisseru, B., Woodruff, A. W. J. clin. Path. 1968, 21, 449. 8. Krupp, I. M. Am. J. trop. Med. Hyg. 1974, 23, 378. 9. Hogarth-Scott, R. S., Feery, B. J. Aust. J. exp. Biol. med. Sci. 1976, 54, 317. 10. de Savigney, D. J. Parasit. 1975, 61, 781. 1.
IS ACEPHYLLINE A THEOPHYLLINE BRONCHODILATOR?
SIR,-For thirty years acephylline piperazine (acepiphylhas been used in many countries for the treatment of asthma. The drug is listed as a theophylline derivative, with uses similarly to those of aminophylline. The 1972 edition of "Martindale"’ citing Turner-Warwick,2stated that 850 mg of acephylline piperazine is equivalent in theophylline content to 600 mg aminophylline. However, Turner-Warwick measured serum concentrations by a spectrophotometric method3 which is not specific (most xanthine derivatives show a similar absorption curve); furthermore acephylline extraction is low at pH values recommended.3 Acephylline is 1,3-dimethylxanthinyylacetic acid, so it is an N-7 substituted theophylline derivative. To test the statement that theophylline is the active metabolite of acephylline we did studies in healthy volunteers and in one patient on daily acepiphylline. Theophylline and acephylline were determined in urine by gas/liquid chromatography and in blood by our method.4 Acephylline, in contrast to aminophylline and choline theophyllinate, did not dissociate to theophylline. In the second part of our study we looked at the pharmacokinetics of acephylline. A volunteer was injected intravenously with acephylline (acephylline piperazine 5 ml 500 mg). The serum-concentration/time curve was biphasic with t2values of 11 and 47 min, giving an apparent volume of distribution of 0-45 lay and a clearance-rate of 408 ml/kg/h. After 4 h the total dose of acephylline had been recovered from the urine. We could find no trace of theophylline or other xanthine metabolites in serum or urine. After oral administration of 500 mg acephylline piperazine to volunteers no acephylline was detected in the serum, and only traces were found in the urine. After 8 h 1-4% of the total dose of acephylline was recovered in the urine. When the urine was hydrolysed by acid and heat, the maximum concentration of acephylline was 2.4%. Again, neither theophylline nor other xanthines were found. A patient who had been taking a compound tablet of acephylline piperazine with phenobarbitone three times a day for months was investigated. No acephylline was found in serum 1 h after taking a tablet (250 mg acephylline piperazine and 17.5mg phenobarbitone), nor after taking a syrup (15 ml containing 300 mg acephylline piperazine and 10 mg phenobarbitone) which is reputed to be better absorbed. Phenobarbitone serum levels were 13.8 and 13-6 fLg/ml, respectively, producing a sedative effect. These findings show that acephylline given intravenously is completely eliminated via the kidney within 4 h and that absorption after oral administration is very poor, as it is in animals.s No theophylline or other xanthine derivatives were detected in serum or urine. It is remarkable that a drug with
line)
=
1. Martindale: the Extra Pharmacopœia; p. 353. London, 1972. 2. Turner-Warwick, M. Br. med. J. 1957, ii, 67. 3. Schack, J., Waxler, S. J. Pharmac. expt. Ther. 1949, 97, 283. 4. Zuidema, J., Merkus, F. W. H. M. J. Chromatogr. 1978, 145, 489. 5. Strolin-Benedetti, M., Lame, D. A., Oliver, Ch., Bouvet, P. Arzneimittel-
forsch. 1974, 24, 662.
51-105).
Basic Sciences Laboratory and M.C.H. Division of Preventive Medicine,
Section,
Ministry of Health, Maputo, Mozambique
ANGELA MELAMED MALCOLM SEGALL
HUMAN TOXOCARA INFECTION IN WEST OF SCOTLAND
PRIST should be used for confirmation of the diagnosis and for the monitoring of antibody levels in relation to duration of infection and antibody response to treatment. We feel that our findings indicate a high prevalence of Toxocara infection and point to the need for more widespread scrutiny of the population so that the true pathological significance of the detection of Toxocara antibodies can be assessed.
Department of Bacteriology, Stobhill General Hospital, Glasgow G21 3UW
R. W. A. GIRDWOOD
Department of Zoology, University of Glasgow
H. V. SMITH R. G. BRUCE R. QUINN
Six,-The pathogenic propensity of Toxocara canis larva: for
first demonstrated in 1952,1 and the public-health of importance Toxocara infection in the U.K. has been extensively reviewed by Woodruff.2-4 T. canis is a common parasite of dogs, and infected dogs excrete large numbers of potentially infective ova into the environment.56However, the prevalence of human infection and, more importantly, the human disease attributable to the parasite remain controversial. The "dog problem" has lately received publicity in the Press and on television in the U.K., and some district councils are setting up schemes for the collection of stray animals. We report here the preliminary findings of a survey of the prevalance of human Toxocara infection in the West of Scotland. Diagnosis of toxocariasis is, with few exceptions, dependent on the demonstration of antibodies to the parasite or its products in the serum of suspected cases. Most surveys of human infection have been based on tests with somatic antigens derived from adult or larval worms.’·8 However, such somatic antigens lack sensitivity and show a high degree of cross-reactivity with Ascaris.9 The development of an in-vitro system for the maintenance of second-stage larvx’O has permitted the harvesting of larval secretions for use as a diagnostic antigen. In the rabbit we have found such a secretory antigen preparation to be both sensitive and specific; there were no cross-reactions between experimentally induced visceral larva migrans of T. canis, Toxascaris leionina, A. lumbricoides and A. suum oriman was
gins. Using counterimmunoelectrophoresis (C.LE.), indirect fluorescent antibody tests (LF.A.), and the paper radioimmunosorbent test (PRIST) we obtained the following results with serea from patients and blood-donors in the West of Scotland:
*
Only 2 of the
13 positive sera were of West of Scotland origin. 1 schistosome, 1 Fasciola, 1
t 4 Ascaris, 3 hookworm, 4 EnterobIUs, Filaria, and 2 Taenia.
with the three tests suggests that the c.i.E. and suitable for rapid screening procedures and that
Experience l.F.A.
are
Beaver, P. C., Snyder, C. H., Carrera, G. M., Dent, J. H., Lafferty, J. W Pediatrics, 1952, 9, 7. 2. Woodruff, A. W. Br. med. J. 1970, iii, 663. 3. Woodruff, A. W. Br. vet. J. 1975, 131, 627. 4. Woodruff, A. W. Envir. Hlth, 1976, 1, 29. 5. Girdwood, R. W. A., Quinn, R., Smith, H. V., Bruce, R. G., Trans. R. Soc. trop. Med. Hyg. 1976, 70, 284. 6. Jacobs, D. E., Pegg, E. J., Stevenson, P. J. Small Anim. Pract 1977, 18, 79. 7. Bisseru, B., Woodruff, A. W. J. clin. Path. 1968, 21, 449. 8. Krupp, I. M. Am. J. trop. Med. Hyg. 1974, 23, 378. 9. Hogarth-Scott, R. S., Feery, B. J. Aust. J. exp. Biol. med. Sci. 1976, 54, 317. 10. de Savigney, D. J. Parasit. 1975, 61, 781. 1.
IS ACEPHYLLINE A THEOPHYLLINE BRONCHODILATOR?
SIR,-For thirty years acephylline piperazine (acepiphylhas been used in many countries for the treatment of asthma. The drug is listed as a theophylline derivative, with uses similarly to those of aminophylline. The 1972 edition of "Martindale"’ citing Turner-Warwick,2stated that 850 mg of acephylline piperazine is equivalent in theophylline content to 600 mg aminophylline. However, Turner-Warwick measured serum concentrations by a spectrophotometric method3 which is not specific (most xanthine derivatives show a similar absorption curve); furthermore acephylline extraction is low at pH values recommended.3 Acephylline is 1,3-dimethylxanthinyylacetic acid, so it is an N-7 substituted theophylline derivative. To test the statement that theophylline is the active metabolite of acephylline we did studies in healthy volunteers and in one patient on daily acepiphylline. Theophylline and acephylline were determined in urine by gas/liquid chromatography and in blood by our method.4 Acephylline, in contrast to aminophylline and choline theophyllinate, did not dissociate to theophylline. In the second part of our study we looked at the pharmacokinetics of acephylline. A volunteer was injected intravenously with acephylline (acephylline piperazine 5 ml 500 mg). The serum-concentration/time curve was biphasic with t2values of 11 and 47 min, giving an apparent volume of distribution of 0-45 lay and a clearance-rate of 408 ml/kg/h. After 4 h the total dose of acephylline had been recovered from the urine. We could find no trace of theophylline or other xanthine metabolites in serum or urine. After oral administration of 500 mg acephylline piperazine to volunteers no acephylline was detected in the serum, and only traces were found in the urine. After 8 h 1-4% of the total dose of acephylline was recovered in the urine. When the urine was hydrolysed by acid and heat, the maximum concentration of acephylline was 2.4%. Again, neither theophylline nor other xanthines were found. A patient who had been taking a compound tablet of acephylline piperazine with phenobarbitone three times a day for months was investigated. No acephylline was found in serum 1 h after taking a tablet (250 mg acephylline piperazine and 17.5mg phenobarbitone), nor after taking a syrup (15 ml containing 300 mg acephylline piperazine and 10 mg phenobarbitone) which is reputed to be better absorbed. Phenobarbitone serum levels were 13.8 and 13-6 fLg/ml, respectively, producing a sedative effect. These findings show that acephylline given intravenously is completely eliminated via the kidney within 4 h and that absorption after oral administration is very poor, as it is in animals.s No theophylline or other xanthine derivatives were detected in serum or urine. It is remarkable that a drug with
line)
=
1. Martindale: the Extra Pharmacopœia; p. 353. London, 1972. 2. Turner-Warwick, M. Br. med. J. 1957, ii, 67. 3. Schack, J., Waxler, S. J. Pharmac. expt. Ther. 1949, 97, 283. 4. Zuidema, J., Merkus, F. W. H. M. J. Chromatogr. 1978, 145, 489. 5. Strolin-Benedetti, M., Lame, D. A., Oliver, Ch., Bouvet, P. Arzneimittel-
forsch. 1974, 24, 662.
