363
left hemisphere and the obverse side of the coil to stimulate the right hemisphere. Stimulation intensity was increased by 5% increments from subthreshold levels until threshold intensity was reached, defined as the intensity required to produce a motor-evoked potential of at least 100 pV onset-to-peak amplitude in at least three of five consecutive trials. The study protocol was approved by the Austin Hospital ethics committee. Patients with untreated epilepsy had a significantly lower mean threshold than controls whilst patients with treated epilepsy had significantly higher mean thresholds: Mean threshold zoo)*
Group
In 1991, therefore, we are exactly where we were in 1971. We again use SK, systemically, up to 12 h after infarction, assuming that something other than reopening of the vessel reduces mortality. If one assumes that about half of the 500 myocardial infarction patients seen at this hospital every year were eligible for thrombolytic therapy and invasive treatment, the interventional procedures and tissue plasminogen activation in these patients ($1500 for coronary arteriography and angioplasty,$2300 for 100 mg TPA) sum up to a grand total of$19 million over the two decades. Had we stayed with our 1971 regimen of intravenous SK only, the bill would have been only$400 000 and we would have
saved$18-6 million over the past two decades. Division of
Cardiology, University Hospital Graz, *And 95% confidence interval.
tsignificantly different
from controls at
p < 0 001 (t-test, unpaired). No seizures were induced in patients with epilepsy. Our results suggest that cortical excitability is increased in untreated idiopathic generalised epilepsy. Depolarisation of motor cortical neurons by magnetic stimulation with the coil tangential to the scalp is thought to be mainly transynaptic.3 A lower threshold is consistent with a relative excess of excitation over inhibition in the motor cortex in untreated patients, as predicted by the feline model. The findings also indicate that anticonvulsant treatment of generalised epilepsy decreases motor excitability, in keeping with observations in focal epilepsy.4 Finally, our experience shows that transcranial stimulation is safe in people with generalised epilepsy, and it seems to be a novel tool for exploring the pathophysiology of this disorder and, possibly, for monitoring the effects of treatment. Department of Neurology, Hospital, Heidelberg, Victoria 3084, Australia, and Department of Medicine, University of Melbourne
Austin
DAVID C. REUTENS SAMUEL F. BERKOVIC
WERNER KLEIN
A-8036 Graz, Austria
1. Klein W, Pavek P, Brandt D, et al. Resultate einer Doppelblindstudie beirn Myokardinfarkt. In: Die Fibrinolyse-Behandlung des akuten Myokard-Infarktes. Vienna: S. Sailer Verlag Bruder Hollinek, 1976. 2 Rentrop KP, De Vivie ER, Karsch KR, Kreuzer H Acute coronary occlusion with impending infarction as an angiographic complication relieved by a guide wire recanalization. Clin Cardiol 1978; 1: 101. 3. ISAM Study Group a prospective trial of intravenous streptokinase m acute myocardial infarction (ISAM). N Engl J Med 1986; 314: 1465-71. 4. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; i. 397. 5. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; ii: 349. 6. TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial. Circulation 1984; 70: 1012-17. 7. The Thrombolysis and Angioplasty in Acute Myocardial Infarction (TAMI) Trial. In. Topol EJ, ed. In Acute coronary intervention. New York: Alan R. Liss, 1988: 153-74. 8. Gruppo Italiano per lo Studio della Soprauvivenza nell’Infarto Miocardico (GISSI2) a factorial randomised trial of alteplase vs streptokinase and heparin among 12 490 patients with acute myocardial infarction. Lancet 1990; 336: 65-71. 9. ISIS-3. Presentation at 41st meeting of American College of Cardiology (Atlanta,
Georgia, 1991). 1. Meldrum BS. Anatomy, physiology, and pathology of epilepsy. Lancet 1990, 336: 231-34. 2. Gloor P, Avoli M, Kostopoulos G. Thalamo-cortical relationships in generalised epilepsy with bilaterally synchronous spike-and-wave discharge. In: Avoli M, Gloor P, Kostopoulos G, Naquet R, eds. Generalised epilepsy: neurobiological approaches. Boston: Birkhauser Boston, 1990: 190-213. 3. Amassian VE, Cracco RQ, Maccabee PJ. Focal stimulation of human cerebral cortex with the magnetic coil: a comparison with electrical stimulation Electroenceph Clin Neurophysiol 1989; 74: 401-16. 4. Hufnagel A, Elger CE, Marx W, Ising A Magnetic motor-evoked potentials in epilepsy: effects of the disease and of anticonvulsant medications. Ann Neurol 1990; 28: 680-86.
Streptokinase full circle SIR,-In several European hospitals, cardiologists have been using thrombolytic therapy in the treatment of acute myocardial infarction for almost 20 years. In 1971 we used streptokinase (SK) intravenously up to 12 h after the onset of symptoms. The mechanism of action of the fibrinolysis was ascribed to an unloading effect on the heart by decreasing systemic vascular resistance and blood viscosity rather than to the reopening of the occluded vessel.1 In 1978 we learned from Rentrop et alz that occluded coronary vessels can be opened by a guidewire and/or intracoronary SK. We were
told that the intravenous
route was not as
effective
as
the
intracoronary and that intervention up to 12 h was too late. Newer
thrombolytic agents such as alteplase and anistreplase, of greater thrombolytic potency and achieving higher patency rates, were developed, and huge trials were set up to confirm this new concept of ultrafast intervention in acute myocardial infarction. However, the ISAM3, GISSI-I4 and ISIS-25 trials confirmed the efficacy of intravenous SK and demonstrated that the thrombolytic agent was also useful later than 4-6 h. Then the TIMI6 and TAMF trials yielded ample evidence that immediate coronary angiography and angioplasty is not mandatory. Finally, GISSI-2 and ISIS-3 showed that "good old" SK was just as effective as the newer thrombolytic drugs in respect to mortality reduction, which implies that the reopening of the vessel may not be the decisive mechanism, since the newer agents do achieve higher rates of vessel patency. So the notion of the open artery is an issue once more.
Typhoid
in Indonesia
SiR,—Typhoid fever constitutes a huge public health burden in Indonesia. This is called to our attention by a paper by Dr Simanjuntak and his colleagues (Oct 26, p 1055) on the oral Ty2la vaccine. Protective efficacy in that study was about 50%, much less than the 96% found in Egypt with an analogous vaccine and less than the 67% found in people immunised with enteric-coated capsules in Chile. It is suggested that one explanation for the lower protective effect of the vaccine in Indonesia is that immunity is overcome by more frequent inoculations of greater numbers of bacteria. This paper does not deal with the extraordinary density of typhoid fever in Indonesia. One might have speculated that the population at risk was a vulnerable, ghetto-bound homeless one; however, the study was done in Sumatra, on the Pertamina Oil Company compound and 40% of participants lived in company houses with running water and toilets. The other 60% lived outside the compound. Unfortunately, the two populations are lumped together. Previous studies had indicated an annual attack rate in the study group of blood-culture-positive typhoid fever of about 690 per 100 000 yearly, a formidable number. This paper has stirred up memories of my year at Gadjha Mada University in Jogjakarta, central Java, 20 years ago. Here are some vignettes which seem relevant to the spread of typhoid fever in Indonesia. To take advantage of the cool mornings, my wife and I would ride our bicycles at about 5 o’clock along paths bordering mountain streams bringing water down to the terraced rice paddies. At that hour there were already large numbers of people bathing and washing clothes in the running water-an idyllic scene frequently capped by a Rabelaisian touch, for under a bridge in open view would appear a row of naked bottoms awaiting a peristaltic rush to enrich the culture medium downstream. When we visited a school outside Jogjakarta the headmaster was pleased to show us a new latrine in a hidden bower on the bank of a pond. It was so constructed that faeces would fall freely to the pond below, where elegant coprophilic carp were ready and waiting to augment the food chain. On another occasion we joined friends to bathe at a
left hemisphere and the obverse side of the coil to stimulate the right hemisphere. Stimulation intensity was increased by 5% increments from subthreshold levels until threshold intensity was reached, defined as the intensity required to produce a motor-evoked potential of at least 100 pV onset-to-peak amplitude in at least three of five consecutive trials. The study protocol was approved by the Austin Hospital ethics committee. Patients with untreated epilepsy had a significantly lower mean threshold than controls whilst patients with treated epilepsy had significantly higher mean thresholds: Mean threshold zoo)*
Group
In 1991, therefore, we are exactly where we were in 1971. We again use SK, systemically, up to 12 h after infarction, assuming that something other than reopening of the vessel reduces mortality. If one assumes that about half of the 500 myocardial infarction patients seen at this hospital every year were eligible for thrombolytic therapy and invasive treatment, the interventional procedures and tissue plasminogen activation in these patients ($1500 for coronary arteriography and angioplasty,$2300 for 100 mg TPA) sum up to a grand total of$19 million over the two decades. Had we stayed with our 1971 regimen of intravenous SK only, the bill would have been only$400 000 and we would have
saved$18-6 million over the past two decades. Division of
Cardiology, University Hospital Graz, *And 95% confidence interval.
tsignificantly different
from controls at
p < 0 001 (t-test, unpaired). No seizures were induced in patients with epilepsy. Our results suggest that cortical excitability is increased in untreated idiopathic generalised epilepsy. Depolarisation of motor cortical neurons by magnetic stimulation with the coil tangential to the scalp is thought to be mainly transynaptic.3 A lower threshold is consistent with a relative excess of excitation over inhibition in the motor cortex in untreated patients, as predicted by the feline model. The findings also indicate that anticonvulsant treatment of generalised epilepsy decreases motor excitability, in keeping with observations in focal epilepsy.4 Finally, our experience shows that transcranial stimulation is safe in people with generalised epilepsy, and it seems to be a novel tool for exploring the pathophysiology of this disorder and, possibly, for monitoring the effects of treatment. Department of Neurology, Hospital, Heidelberg, Victoria 3084, Australia, and Department of Medicine, University of Melbourne
Austin
DAVID C. REUTENS SAMUEL F. BERKOVIC
WERNER KLEIN
A-8036 Graz, Austria
1. Klein W, Pavek P, Brandt D, et al. Resultate einer Doppelblindstudie beirn Myokardinfarkt. In: Die Fibrinolyse-Behandlung des akuten Myokard-Infarktes. Vienna: S. Sailer Verlag Bruder Hollinek, 1976. 2 Rentrop KP, De Vivie ER, Karsch KR, Kreuzer H Acute coronary occlusion with impending infarction as an angiographic complication relieved by a guide wire recanalization. Clin Cardiol 1978; 1: 101. 3. ISAM Study Group a prospective trial of intravenous streptokinase m acute myocardial infarction (ISAM). N Engl J Med 1986; 314: 1465-71. 4. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; i. 397. 5. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; ii: 349. 6. TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial. Circulation 1984; 70: 1012-17. 7. The Thrombolysis and Angioplasty in Acute Myocardial Infarction (TAMI) Trial. In. Topol EJ, ed. In Acute coronary intervention. New York: Alan R. Liss, 1988: 153-74. 8. Gruppo Italiano per lo Studio della Soprauvivenza nell’Infarto Miocardico (GISSI2) a factorial randomised trial of alteplase vs streptokinase and heparin among 12 490 patients with acute myocardial infarction. Lancet 1990; 336: 65-71. 9. ISIS-3. Presentation at 41st meeting of American College of Cardiology (Atlanta,
Georgia, 1991). 1. Meldrum BS. Anatomy, physiology, and pathology of epilepsy. Lancet 1990, 336: 231-34. 2. Gloor P, Avoli M, Kostopoulos G. Thalamo-cortical relationships in generalised epilepsy with bilaterally synchronous spike-and-wave discharge. In: Avoli M, Gloor P, Kostopoulos G, Naquet R, eds. Generalised epilepsy: neurobiological approaches. Boston: Birkhauser Boston, 1990: 190-213. 3. Amassian VE, Cracco RQ, Maccabee PJ. Focal stimulation of human cerebral cortex with the magnetic coil: a comparison with electrical stimulation Electroenceph Clin Neurophysiol 1989; 74: 401-16. 4. Hufnagel A, Elger CE, Marx W, Ising A Magnetic motor-evoked potentials in epilepsy: effects of the disease and of anticonvulsant medications. Ann Neurol 1990; 28: 680-86.
Streptokinase full circle SIR,-In several European hospitals, cardiologists have been using thrombolytic therapy in the treatment of acute myocardial infarction for almost 20 years. In 1971 we used streptokinase (SK) intravenously up to 12 h after the onset of symptoms. The mechanism of action of the fibrinolysis was ascribed to an unloading effect on the heart by decreasing systemic vascular resistance and blood viscosity rather than to the reopening of the occluded vessel.1 In 1978 we learned from Rentrop et alz that occluded coronary vessels can be opened by a guidewire and/or intracoronary SK. We were
told that the intravenous
route was not as
effective
as
the
intracoronary and that intervention up to 12 h was too late. Newer
thrombolytic agents such as alteplase and anistreplase, of greater thrombolytic potency and achieving higher patency rates, were developed, and huge trials were set up to confirm this new concept of ultrafast intervention in acute myocardial infarction. However, the ISAM3, GISSI-I4 and ISIS-25 trials confirmed the efficacy of intravenous SK and demonstrated that the thrombolytic agent was also useful later than 4-6 h. Then the TIMI6 and TAMF trials yielded ample evidence that immediate coronary angiography and angioplasty is not mandatory. Finally, GISSI-2 and ISIS-3 showed that "good old" SK was just as effective as the newer thrombolytic drugs in respect to mortality reduction, which implies that the reopening of the vessel may not be the decisive mechanism, since the newer agents do achieve higher rates of vessel patency. So the notion of the open artery is an issue once more.
Typhoid
in Indonesia
SiR,—Typhoid fever constitutes a huge public health burden in Indonesia. This is called to our attention by a paper by Dr Simanjuntak and his colleagues (Oct 26, p 1055) on the oral Ty2la vaccine. Protective efficacy in that study was about 50%, much less than the 96% found in Egypt with an analogous vaccine and less than the 67% found in people immunised with enteric-coated capsules in Chile. It is suggested that one explanation for the lower protective effect of the vaccine in Indonesia is that immunity is overcome by more frequent inoculations of greater numbers of bacteria. This paper does not deal with the extraordinary density of typhoid fever in Indonesia. One might have speculated that the population at risk was a vulnerable, ghetto-bound homeless one; however, the study was done in Sumatra, on the Pertamina Oil Company compound and 40% of participants lived in company houses with running water and toilets. The other 60% lived outside the compound. Unfortunately, the two populations are lumped together. Previous studies had indicated an annual attack rate in the study group of blood-culture-positive typhoid fever of about 690 per 100 000 yearly, a formidable number. This paper has stirred up memories of my year at Gadjha Mada University in Jogjakarta, central Java, 20 years ago. Here are some vignettes which seem relevant to the spread of typhoid fever in Indonesia. To take advantage of the cool mornings, my wife and I would ride our bicycles at about 5 o’clock along paths bordering mountain streams bringing water down to the terraced rice paddies. At that hour there were already large numbers of people bathing and washing clothes in the running water-an idyllic scene frequently capped by a Rabelaisian touch, for under a bridge in open view would appear a row of naked bottoms awaiting a peristaltic rush to enrich the culture medium downstream. When we visited a school outside Jogjakarta the headmaster was pleased to show us a new latrine in a hidden bower on the bank of a pond. It was so constructed that faeces would fall freely to the pond below, where elegant coprophilic carp were ready and waiting to augment the food chain. On another occasion we joined friends to bathe at a
