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.
1319 these pharmacokinetic properties has been used for so long for such an important indication. The only thing we do know about acephylline is that it is a N-7 theophylline derivative. The best known of these is caffeine, but this xanthine derivative has none of the pharmacokinetic and pharmacodynamic characteristics of theophylline.6 For theophylline the therapeutic range and dosage regimens are known;’ it is a potent and fast-acting bronchodilator and should be preferred when a xanthine is desired for the suppression of chronic asthmatic symptoms. Department of Biopharmaceutics, Faculty of Medicine and Faculty of Pharmacy, University of Amsterdam, Amsterdam, Netherlands
(i.e.,
to
be in the
same
age-
60) as many patients with chronic pain. Since for chronic pain is transcutaneous nerve stimulation (T.rt.s.)1 there is a chance that a patient with a pacemaker will receive T.N.s. treatment, and vice versa. What are the hazards? T.N.S. stimulation was administered by constant-current stimulator giving 0.2 ms square pulses at frequencies of 10-100 Hz and short trains of such pulses between 1 and 10 Hz.2 The stimulator has a maximal output current of 60 mA with an external load of 2500 Q. The largest current used was 40 mA. Every patient was examined four times with the surface electrodes placed in different positions used in common chronic pain conditions (thoracic, paravertebral lumbar, lumbar-sciatic, and distal on the lower extremity). Eight patients have been tested so far. Six had synchronous pacemakers: four were of the ventricular-inhibited type (Siemens-Elema EM 157/70, EM 207/70, Variopacemaker EM 159, and CPI PG 0505), one was ventricular triggered (EM 153/70), and one was atrial synchronous (EM 155/50). The remaining two patients had a synchronous (fixed-rate) pacemaker (EM 152/70). The ventricular-inhibited pacemaker stays inhibited as long as the patient’s heart is in spontaneous ventricular rhythm faster than the pacing-rate of the pulse generator. When the spontaneous heart-rate drops, the pulse generator will begin and continue pacing until the patient’s heart-rate again increases above the rate of the pulse generator. Pacemakers of this type are the more common. All four pacemakers of this type were totally blocked by T.N.S. stimulation of 1-3 Hz, in one case up to 6 Hz (see figure). The frequency variation depends on what type of protective filter against electromagnetic interference the pacemaker is equipped with. The current needed for blocking was only 5 mA with the electrodes on the thoracic wall, whereas with the lumbar-sciatic position 10 mA was needed. Therapeutic current intensities are usually 20-40 mA. With the electrodes in the distal position on the extremity there was no blocking, nor did we find any blocking with frequencies above 6 Hz. However, T.N.S. stimulation of higher frequencies could well cause blocking of a ventricular-inhibited pacemaker if electrode-skin contact were par or if the T.N.s. stimulator were malfunctioning. The ventricular-triggered pacemaker senses and is triggered by spontaneous ventricular activity and fires an impulse in response to it. This impulse is superimposed on the QRS-complex and does not initiate independent ventricular depolarisation. If spontaneous activity ceases, the pulse generator gives out an impulse after a preset interval and continues to do so until spontaneous heart activity is resumed. This type of pacemaker group
over
one treatment
6. 7. 1 2.
triggered by the T.N.s.-stimulator at all frequencies above 2 Hz, which gave the patient a heart-rate of up to 130/min, the upper limit of the pacemaker. The atrial synchronous pacemaker instead senses atrial electrical activity and after a suitable delay triggers an impulse to the ventricle, depolarising it. T.N.S. stimulation triggered the pacemaker up to its peak rate was
J. ZUIDEMA F. W. H. M. MERKUS
HAZARD FROM TRANSCUTANEOUS NERVE STIMULATION IN PATIENTS WITH PACEMAKERS
SIR,-Patients with pacemakers tend
Ventricular-inhibited pacemaker: T.N.S. electrodes in paravertebral, lumbar position. The pacemaker function is completely blocked by 2 Hz, 10 mA transcutaneous nerve stimulation.
Mitenko, P. A., Ogilvie, R. I. Clin. Pharmac. Ther. 1973, 14, 509. Weinberger, M., Hendeles, L. Am. J. Hosp. Pharm. 1976, 33, 1071. Shealy, C. N., Maurer, D. Surg. Neurol. 1974, 2, 45. Eriksson, M., Sjölund, B. in Sensory Functions of the Skin (edited by Y. Zotterman); p. 575. Oxford, 1976.
ofl50/min. The interference between a T.N.S. stimulator and a synchpacemaker is due to the synchronous pacemaker being unable to "separate" externally applied electrical signals from spontaneous cardiac activity. The asynchronous (fixed-rate) pacemaker, delivers electrical impulses at a constant rate, usually set at 70/min. The presence of spontaneous cardiac activity does not affect the pacemaker at all. This type of pacemaker could neither be blocked nor triggered by T.N.S. stimulation with any frequency at maximal current intensity. Our findings suggest that T.N.s. is contraindicated in patients with cardiac pacemaker of synchronous type (ventricular inhibited, ventricular triggered, atrial synchronous but that T.N.S. can be given without risk to patients with an asynchronous (fixedronous
rate) pacemaker. Departments of Clinical Neurophysiology, Thoracic Surgery, and Neurosurgery, University of Lund, S-221 85 Lund, Sweden
MARGARETA ERIKSSON HANS SCHÜLLER BENGT SJÖLUND
VASA VASORUM AND CORONARY ATHEROSCLEROSIS
SiR,—Koster in 1875 concluded from the study of serial sections that arteriosclerosis involves the arterial wall by way of the vasa vasorum. Re-examination of this old idea is suggested by the recent finding that platelets play an essential role in atherogenesis.2,3 Morphological studies have pinpointed the site of origin of the coronary atheroma as just beneath the internal elastic lamina; smooth-muscle cells are believed to invade the intima through clefts in the lamina.4-6 The requirement of platelets for atherogenesis is believed to be due to their providing a factor essential for proliferation of smooth-muscle cells.’ Would this platelet growth factor best reach the developing atheroma by diffusion from the lumen of the artery or through the vasa vasorum? Atheromas contain vessels which sometimes manifest as hoemorrhages .8,9 Penetration of the adventitial vasa vasorum to the internal elastic lamina of a normal artery has been demonstrated only for the aorta of the horse. 10 The coronary vasa vasorum are anatomically connected 1. Köster, W. Berlin Klin. Wschr. 1875, 13, 454. 2. Moore, S., Friedman, R. J., Singal, D P., Gauldie, J., Blajchman, M. Thromb. Diath. Hœmorrh. 1976, 35, 70. 3. Fuster, V., Bowie, E. J. W., Lewis, J. C. Thromb. Hœmostas. 1977, 38, 55. 4. Moon, H. D., Rinehart, J. F. Circulation, 1952, 6, 481. 5. Ross, R., Glomset, J., Harker, L. Am. J. Path. 1977, 86, 675. 6. Hartman, J. D. ibid. 1977, 89, 13. 7. Ross, R., Glomset, J., Kariya, B., Harker, L. Proc. natn Acad. Sci U.S.A.
1974, 71, 1207. 8. 9
Wartman, W. B. Am Heart J. 1938, 15, 459. Gottfried, M., Yao, J., Glagov, S. Fedn Proc. 1978, 37, 933.
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.
1319 these pharmacokinetic properties has been used for so long for such an important indication. The only thing we do know about acephylline is that it is a N-7 theophylline derivative. The best known of these is caffeine, but this xanthine derivative has none of the pharmacokinetic and pharmacodynamic characteristics of theophylline.6 For theophylline the therapeutic range and dosage regimens are known;’ it is a potent and fast-acting bronchodilator and should be preferred when a xanthine is desired for the suppression of chronic asthmatic symptoms. Department of Biopharmaceutics, Faculty of Medicine and Faculty of Pharmacy, University of Amsterdam, Amsterdam, Netherlands
(i.e.,
to
be in the
same
age-
60) as many patients with chronic pain. Since for chronic pain is transcutaneous nerve stimulation (T.rt.s.)1 there is a chance that a patient with a pacemaker will receive T.N.s. treatment, and vice versa. What are the hazards? T.N.S. stimulation was administered by constant-current stimulator giving 0.2 ms square pulses at frequencies of 10-100 Hz and short trains of such pulses between 1 and 10 Hz.2 The stimulator has a maximal output current of 60 mA with an external load of 2500 Q. The largest current used was 40 mA. Every patient was examined four times with the surface electrodes placed in different positions used in common chronic pain conditions (thoracic, paravertebral lumbar, lumbar-sciatic, and distal on the lower extremity). Eight patients have been tested so far. Six had synchronous pacemakers: four were of the ventricular-inhibited type (Siemens-Elema EM 157/70, EM 207/70, Variopacemaker EM 159, and CPI PG 0505), one was ventricular triggered (EM 153/70), and one was atrial synchronous (EM 155/50). The remaining two patients had a synchronous (fixed-rate) pacemaker (EM 152/70). The ventricular-inhibited pacemaker stays inhibited as long as the patient’s heart is in spontaneous ventricular rhythm faster than the pacing-rate of the pulse generator. When the spontaneous heart-rate drops, the pulse generator will begin and continue pacing until the patient’s heart-rate again increases above the rate of the pulse generator. Pacemakers of this type are the more common. All four pacemakers of this type were totally blocked by T.N.S. stimulation of 1-3 Hz, in one case up to 6 Hz (see figure). The frequency variation depends on what type of protective filter against electromagnetic interference the pacemaker is equipped with. The current needed for blocking was only 5 mA with the electrodes on the thoracic wall, whereas with the lumbar-sciatic position 10 mA was needed. Therapeutic current intensities are usually 20-40 mA. With the electrodes in the distal position on the extremity there was no blocking, nor did we find any blocking with frequencies above 6 Hz. However, T.N.S. stimulation of higher frequencies could well cause blocking of a ventricular-inhibited pacemaker if electrode-skin contact were par or if the T.N.s. stimulator were malfunctioning. The ventricular-triggered pacemaker senses and is triggered by spontaneous ventricular activity and fires an impulse in response to it. This impulse is superimposed on the QRS-complex and does not initiate independent ventricular depolarisation. If spontaneous activity ceases, the pulse generator gives out an impulse after a preset interval and continues to do so until spontaneous heart activity is resumed. This type of pacemaker group
over
one treatment
6. 7. 1 2.
triggered by the T.N.s.-stimulator at all frequencies above 2 Hz, which gave the patient a heart-rate of up to 130/min, the upper limit of the pacemaker. The atrial synchronous pacemaker instead senses atrial electrical activity and after a suitable delay triggers an impulse to the ventricle, depolarising it. T.N.S. stimulation triggered the pacemaker up to its peak rate was
J. ZUIDEMA F. W. H. M. MERKUS
HAZARD FROM TRANSCUTANEOUS NERVE STIMULATION IN PATIENTS WITH PACEMAKERS
SIR,-Patients with pacemakers tend
Ventricular-inhibited pacemaker: T.N.S. electrodes in paravertebral, lumbar position. The pacemaker function is completely blocked by 2 Hz, 10 mA transcutaneous nerve stimulation.
Mitenko, P. A., Ogilvie, R. I. Clin. Pharmac. Ther. 1973, 14, 509. Weinberger, M., Hendeles, L. Am. J. Hosp. Pharm. 1976, 33, 1071. Shealy, C. N., Maurer, D. Surg. Neurol. 1974, 2, 45. Eriksson, M., Sjölund, B. in Sensory Functions of the Skin (edited by Y. Zotterman); p. 575. Oxford, 1976.
ofl50/min. The interference between a T.N.S. stimulator and a synchpacemaker is due to the synchronous pacemaker being unable to "separate" externally applied electrical signals from spontaneous cardiac activity. The asynchronous (fixed-rate) pacemaker, delivers electrical impulses at a constant rate, usually set at 70/min. The presence of spontaneous cardiac activity does not affect the pacemaker at all. This type of pacemaker could neither be blocked nor triggered by T.N.S. stimulation with any frequency at maximal current intensity. Our findings suggest that T.N.s. is contraindicated in patients with cardiac pacemaker of synchronous type (ventricular inhibited, ventricular triggered, atrial synchronous but that T.N.S. can be given without risk to patients with an asynchronous (fixedronous
rate) pacemaker. Departments of Clinical Neurophysiology, Thoracic Surgery, and Neurosurgery, University of Lund, S-221 85 Lund, Sweden
MARGARETA ERIKSSON HANS SCHÜLLER BENGT SJÖLUND
VASA VASORUM AND CORONARY ATHEROSCLEROSIS
SiR,—Koster in 1875 concluded from the study of serial sections that arteriosclerosis involves the arterial wall by way of the vasa vasorum. Re-examination of this old idea is suggested by the recent finding that platelets play an essential role in atherogenesis.2,3 Morphological studies have pinpointed the site of origin of the coronary atheroma as just beneath the internal elastic lamina; smooth-muscle cells are believed to invade the intima through clefts in the lamina.4-6 The requirement of platelets for atherogenesis is believed to be due to their providing a factor essential for proliferation of smooth-muscle cells.’ Would this platelet growth factor best reach the developing atheroma by diffusion from the lumen of the artery or through the vasa vasorum? Atheromas contain vessels which sometimes manifest as hoemorrhages .8,9 Penetration of the adventitial vasa vasorum to the internal elastic lamina of a normal artery has been demonstrated only for the aorta of the horse. 10 The coronary vasa vasorum are anatomically connected 1. Köster, W. Berlin Klin. Wschr. 1875, 13, 454. 2. Moore, S., Friedman, R. J., Singal, D P., Gauldie, J., Blajchman, M. Thromb. Diath. Hœmorrh. 1976, 35, 70. 3. Fuster, V., Bowie, E. J. W., Lewis, J. C. Thromb. Hœmostas. 1977, 38, 55. 4. Moon, H. D., Rinehart, J. F. Circulation, 1952, 6, 481. 5. Ross, R., Glomset, J., Harker, L. Am. J. Path. 1977, 86, 675. 6. Hartman, J. D. ibid. 1977, 89, 13. 7. Ross, R., Glomset, J., Kariya, B., Harker, L. Proc. natn Acad. Sci U.S.A.
1974, 71, 1207. 8. 9
Wartman, W. B. Am Heart J. 1938, 15, 459. Gottfried, M., Yao, J., Glagov, S. Fedn Proc. 1978, 37, 933.
