1205
Staggering may also be due to an infectious disease. The other two signs usually are not. Therefore, the clinical signs used by Cook et al. to study neurological illness in dogs may point to a variety of non-infectious and/or non-neurological diseases. Cook et al. state that the temporal sequence of ill dog followed by ill human must be considered important. However, they asked patients about events only up to the age of clinical onset. This precludes their investigating the possibility of M.S. patients transmitting disease to their animals (ill human preceding ill dog). nature.
acute changes in the renin-angiotensin system caused by each exchange procedure. Whether changes in viscosity2 described by Dr Talpos and colleagues (Feb. 25, p. 416) are related to the hypotensive effect of plasma exchange remains to be deter-
mined.
Department of Nephrology, Royal Melbourne Hospital and Department of Physiology, University of Melbourne, Australia
JUDITH A. WHITWORTH A. J. F. D’APICE PRISCILLA KINCAID-SMITH A. A. SHULKES S. L. SKINNER
Neurologic Disease Epidemiologic Study, School of Public Health,
CONSTANCE BARASCH SULLIVAN 90024, U.S.A. ROBERT W. HAILE
University of California, Los Angeles, California
DIABETES WITHOUT GLUCAGON on the diabetogenic role of pancreatic glucagon contradictory. The hypothesis of Unger and Orci’ that glucagon is essential for endogenous hyperglycaemia has been questioned by the investigations of Barnes and Bloom,2 who found no circulating immunoreactive glucagon (I.R.G.) in either the basal state or after arginine stimulation in five pancreatectomised patients with fasting hyperglycxmia. On the other hand Palmer et a1.3 found in a pancreatectomised patient that arginine increased the small-molecular-weight fraction of I.R.G. and plasma-glucose. This finding suggests an extrapancreatic source of biologically active glucagon in man. I have investigated the effect of arginine in eleven patients who had had total surgical pancreatectomy (three females, eight males aged 35-65) after a 14 h fast. Mean daily lente insulin dosage was 28 units. Baseline blood-samples were taken 10 min before arginine infusion (arginine hydrochloride, 500 mg/min/kg body-weight, infused at a constant rate for 30 min) and just before infusion. More blood-samples were collected
S:R,—Views
are
ANTIHYPERTENSIVE EFFECT OF PLASMA EXCHANGE
SIR,-While treating patients with glomerulonephritis by plasma exchange, we noted that the requirements for hypotensive drug therapy were reduced. Sixteen patients with glomerulonephritis and hypertension were treated with plasma exchange over a period of 10 days or more. In ten, hypotensive therapy had to be withdrawn or reduced over the period of plasma exchange. A patient with severe essential hypertension and normal renal function was investigated in detail. The patient was a 38-year-old woman, whose blood-pressure over 3 days averaged 234/149 mm Hg (ambulatory) and 206/133 (on the third day of bed rest) despite daily hypotensive-therapy. Daily drug therapy during this period was prazosin (30 mg), hydrallazine (150 mg), propranolol (480 mg), labetalol (1800 mg), diazoxide (600 mg), chlorothiazide (1 g), spironolactone (200 mg), and minoxidil 30 mg. Fourteen plasma exchanges of 4 litres were done over 22 days. Sitting bloodpressure fell to 155/102 (average over 1 day) after the first four consecutive daily plasma exchanges and at this stage all hypotensive therapy was stopped. Without plasma exchange for the next 3 days blood-pressure rose to 202/124 but fell again after its reintroduction. On completion of fourteen plasma exchanges propranolol (80 mg/day) and frusemide (80 mg/day) were given and blood-pressure was maintained between 125/80 and 160/110 for 1 month. Additional hypotensive therapy then became necessary. The hypotensive effect of plasma exchange, which persisted for several weeks, did not relate to changes in body-weight (58.7 - 60.3 kg), blood-volume (4.4 - 4. litres), plasma-albumin, total plasma-protein concentration, urinary volume, or sodium excretion. Plasma-renin concentration (P.R.C.)’ was high normal at first (63 i.u./ml) and fell when drug therapy was stopped after blood-pressures had reduced.p.R.c. was thus not related directly to the change in blood-pressure. Before drug therapy was stopped, P.R.C. generally increased over a single exchange, but after drug withdrawal P.R.C. fell over each exchange. Plasma-renin substrate (P.R.S.) levels fell with each exchange (59+4%. n=14) but increased again between exchanges towards the initial pre-exchange value of 840 pmol angiotensinI (AI)/ml without a direct relationship to bloodpressure. The lowest post-exchange P.R.S. level was 140 pmol Al/ml. Plasma-renin activity, the value resulting from the invitro reaction between P.R.C. and P.R.S., was normal at first (1 pmol AI/ml/h) and fell over all but two exchanges (first and third), returning to control values by the next exchange. In summary, plasma exchange had a moderately prolonged hypotensive effect in a woman with severe essential hypertension. The effect could not be explained by either plasma or extracellular fluid-volume depletion nor by the considerable 1.
Stockigt, J. R., Collins, 175.
R.
D., Biglieri, E. G. Circ
Res.
1971, 27, suppl. 11,
at
5, 10, 20, 30, 40, 60, 90, 120, and 180 min and
were ana-
for plasma levels of glucagon, glucose, C-peptide, and insulin. Insulin antibodies prevented insulin measurement in all but three patients. None of the plasma components showed significant changes during or after arginine infusion. Plasma-C-peptide was unmeasurable. High levels of I.R.G. were found in the plasma of all eleven patients (71 ±19 pg/ml). Similar results were reported by others.4,5 These basal I.R.G. levels may be high because the antiserum (30 K) has a high basal blank value.6-8 Because there was no stimulation after arginine infusion, these patients appeared to have no extrapancreatic sources of true
lysed
pancreatic glucagon. Nine of the patients
had fasting hyperglycxmia (269::t109 and two had no hyperglycsemia (103±3 mg/dl). Although in one of these non-hyperglycaemic patients no insulin was detected by radioimmunoassay a residual effect of the lente insulin taken 24 h before the investigations could not be excluded. The non-hyperglycaemic patients were therefore reinvestigated. Before a 36 h fast short-acting insulin was given intravenously over 3 days. At the beginning of the fasting period the patients had a mean blood-glucose of 246 mg/dl; after the 36 h fast it was 447 mg/dl. These results thus support Barnes’ and Bloom’s hypothesis2 that the fundamental cause of hyperglycaemia in insulin-dependent diabetics is the failure of the beta cell to produce insulin.
mg/dl)
I Medizinische Universtätsklinik, 2000 Hamburg 20, Germany
Diabetes-Fortschungsinstitut, 4000 Dusseldorf 1.
H. G. DAMMANN J. KUHHALL
H. DROST
1. Unger, R. H., Orci, L. Lancet, 1975, i, 14. 2. Barnes, A. J., Bloom, S. R. ibid. 1976, i, 219. 3. Palmer, J. P., Werner, P. L., Benson, J. W., Ensinck, J. W. ibid. p. 1290. 4. Müller, W., Brennan, M., Tan, M., Aoki, T. Diabetes, 1974, 23, 512. 5. Villanueva, M. L., Hedo, J. A., Marco, J. Diabetologia, 1976, 12, 613. 6. Valverde, I., Villanueva, M. L., Lozano, I., Marco, J. J. clin. Endocr. 1974,
7. 8.
39, 1090. Weir, G. C., Turner, R. C., Martin, D. B. Horm. Metab. Res. 1973, 5, 241. Weir, G. C., Knowlton, S. D., Martin, D. B. J. clin. Endocr. 1975, 40, 296.
Staggering may also be due to an infectious disease. The other two signs usually are not. Therefore, the clinical signs used by Cook et al. to study neurological illness in dogs may point to a variety of non-infectious and/or non-neurological diseases. Cook et al. state that the temporal sequence of ill dog followed by ill human must be considered important. However, they asked patients about events only up to the age of clinical onset. This precludes their investigating the possibility of M.S. patients transmitting disease to their animals (ill human preceding ill dog). nature.
acute changes in the renin-angiotensin system caused by each exchange procedure. Whether changes in viscosity2 described by Dr Talpos and colleagues (Feb. 25, p. 416) are related to the hypotensive effect of plasma exchange remains to be deter-
mined.
Department of Nephrology, Royal Melbourne Hospital and Department of Physiology, University of Melbourne, Australia
JUDITH A. WHITWORTH A. J. F. D’APICE PRISCILLA KINCAID-SMITH A. A. SHULKES S. L. SKINNER
Neurologic Disease Epidemiologic Study, School of Public Health,
CONSTANCE BARASCH SULLIVAN 90024, U.S.A. ROBERT W. HAILE
University of California, Los Angeles, California
DIABETES WITHOUT GLUCAGON on the diabetogenic role of pancreatic glucagon contradictory. The hypothesis of Unger and Orci’ that glucagon is essential for endogenous hyperglycaemia has been questioned by the investigations of Barnes and Bloom,2 who found no circulating immunoreactive glucagon (I.R.G.) in either the basal state or after arginine stimulation in five pancreatectomised patients with fasting hyperglycxmia. On the other hand Palmer et a1.3 found in a pancreatectomised patient that arginine increased the small-molecular-weight fraction of I.R.G. and plasma-glucose. This finding suggests an extrapancreatic source of biologically active glucagon in man. I have investigated the effect of arginine in eleven patients who had had total surgical pancreatectomy (three females, eight males aged 35-65) after a 14 h fast. Mean daily lente insulin dosage was 28 units. Baseline blood-samples were taken 10 min before arginine infusion (arginine hydrochloride, 500 mg/min/kg body-weight, infused at a constant rate for 30 min) and just before infusion. More blood-samples were collected
S:R,—Views
are
ANTIHYPERTENSIVE EFFECT OF PLASMA EXCHANGE
SIR,-While treating patients with glomerulonephritis by plasma exchange, we noted that the requirements for hypotensive drug therapy were reduced. Sixteen patients with glomerulonephritis and hypertension were treated with plasma exchange over a period of 10 days or more. In ten, hypotensive therapy had to be withdrawn or reduced over the period of plasma exchange. A patient with severe essential hypertension and normal renal function was investigated in detail. The patient was a 38-year-old woman, whose blood-pressure over 3 days averaged 234/149 mm Hg (ambulatory) and 206/133 (on the third day of bed rest) despite daily hypotensive-therapy. Daily drug therapy during this period was prazosin (30 mg), hydrallazine (150 mg), propranolol (480 mg), labetalol (1800 mg), diazoxide (600 mg), chlorothiazide (1 g), spironolactone (200 mg), and minoxidil 30 mg. Fourteen plasma exchanges of 4 litres were done over 22 days. Sitting bloodpressure fell to 155/102 (average over 1 day) after the first four consecutive daily plasma exchanges and at this stage all hypotensive therapy was stopped. Without plasma exchange for the next 3 days blood-pressure rose to 202/124 but fell again after its reintroduction. On completion of fourteen plasma exchanges propranolol (80 mg/day) and frusemide (80 mg/day) were given and blood-pressure was maintained between 125/80 and 160/110 for 1 month. Additional hypotensive therapy then became necessary. The hypotensive effect of plasma exchange, which persisted for several weeks, did not relate to changes in body-weight (58.7 - 60.3 kg), blood-volume (4.4 - 4. litres), plasma-albumin, total plasma-protein concentration, urinary volume, or sodium excretion. Plasma-renin concentration (P.R.C.)’ was high normal at first (63 i.u./ml) and fell when drug therapy was stopped after blood-pressures had reduced.p.R.c. was thus not related directly to the change in blood-pressure. Before drug therapy was stopped, P.R.C. generally increased over a single exchange, but after drug withdrawal P.R.C. fell over each exchange. Plasma-renin substrate (P.R.S.) levels fell with each exchange (59+4%. n=14) but increased again between exchanges towards the initial pre-exchange value of 840 pmol angiotensinI (AI)/ml without a direct relationship to bloodpressure. The lowest post-exchange P.R.S. level was 140 pmol Al/ml. Plasma-renin activity, the value resulting from the invitro reaction between P.R.C. and P.R.S., was normal at first (1 pmol AI/ml/h) and fell over all but two exchanges (first and third), returning to control values by the next exchange. In summary, plasma exchange had a moderately prolonged hypotensive effect in a woman with severe essential hypertension. The effect could not be explained by either plasma or extracellular fluid-volume depletion nor by the considerable 1.
Stockigt, J. R., Collins, 175.
R.
D., Biglieri, E. G. Circ
Res.
1971, 27, suppl. 11,
at
5, 10, 20, 30, 40, 60, 90, 120, and 180 min and
were ana-
for plasma levels of glucagon, glucose, C-peptide, and insulin. Insulin antibodies prevented insulin measurement in all but three patients. None of the plasma components showed significant changes during or after arginine infusion. Plasma-C-peptide was unmeasurable. High levels of I.R.G. were found in the plasma of all eleven patients (71 ±19 pg/ml). Similar results were reported by others.4,5 These basal I.R.G. levels may be high because the antiserum (30 K) has a high basal blank value.6-8 Because there was no stimulation after arginine infusion, these patients appeared to have no extrapancreatic sources of true
lysed
pancreatic glucagon. Nine of the patients
had fasting hyperglycxmia (269::t109 and two had no hyperglycsemia (103±3 mg/dl). Although in one of these non-hyperglycaemic patients no insulin was detected by radioimmunoassay a residual effect of the lente insulin taken 24 h before the investigations could not be excluded. The non-hyperglycaemic patients were therefore reinvestigated. Before a 36 h fast short-acting insulin was given intravenously over 3 days. At the beginning of the fasting period the patients had a mean blood-glucose of 246 mg/dl; after the 36 h fast it was 447 mg/dl. These results thus support Barnes’ and Bloom’s hypothesis2 that the fundamental cause of hyperglycaemia in insulin-dependent diabetics is the failure of the beta cell to produce insulin.
mg/dl)
I Medizinische Universtätsklinik, 2000 Hamburg 20, Germany
Diabetes-Fortschungsinstitut, 4000 Dusseldorf 1.
H. G. DAMMANN J. KUHHALL
H. DROST
1. Unger, R. H., Orci, L. Lancet, 1975, i, 14. 2. Barnes, A. J., Bloom, S. R. ibid. 1976, i, 219. 3. Palmer, J. P., Werner, P. L., Benson, J. W., Ensinck, J. W. ibid. p. 1290. 4. Müller, W., Brennan, M., Tan, M., Aoki, T. Diabetes, 1974, 23, 512. 5. Villanueva, M. L., Hedo, J. A., Marco, J. Diabetologia, 1976, 12, 613. 6. Valverde, I., Villanueva, M. L., Lozano, I., Marco, J. J. clin. Endocr. 1974,
7. 8.
39, 1090. Weir, G. C., Turner, R. C., Martin, D. B. Horm. Metab. Res. 1973, 5, 241. Weir, G. C., Knowlton, S. D., Martin, D. B. J. clin. Endocr. 1975, 40, 296.
