36 Continuous metiamide therapy, in a dose of 200 mg. four times daily, produced a dramatic response, with disappearance of symptoms in 9 days. Repeat endoscopy demonstrated healing of the jejunal ulcer after one month, and the stomal ulcer after two months. This was associated with a fall in the serum-gastrin to 235 pg. per ml. after two months, which rose again to 825 pg. per ml. after four months.
The non-invasive diagnosis of the Zollinger-Ellison syndrome hinges on the secretin test: a marked rise in a serum-gastrin, which is almost all big " gastrin, is very suggestive of a tumour. This test does require further evaluation before its routine use can be accepted. The therapeutic effect of metiamide in this case was dramatic, suggesting a major therapeutic role for metiamide in patients with refractory peptic ulceration, and possibly in the Zollinger-Ellison syndrome. We are at a loss to explain the striking changes in the fasting serum-gastrin during therapy, but they were greater than any of the day-to-day variations we have seen in this patient. Another two similar patients have been treated with
not contribute to cerebral symptoms and it is serious problem in acute falciparum malarias treated adequately in the endemic area.
tion does not a
Ramathibodi
Hospital, Bangkok 4, and Phrabudhabat Hospital, Saraburi, Thailand.
"
metiamide over a shorter period. The initial response assessed symptomatically and endoscopically was as good as in the above patient. Department of Surgery, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 4LP. Sunderland Royal Infirmary, Sunderland, Co. Durham.
Department of Physiology, University of Newcastle upon Tyne.
M. H. THOMPSON C. W. VENABLES. I. T. J. D. D. J. E. R. E. L.
MILLER.
REED SANDERS GRUND BLAIR.
INTRAVASCULAR COAGULATION AND MALARIA
conflicting reports 14 of the incidence of increased intravascular coagulation in malaria. Most reports of increased intravascular coagulation came from selected groups of hospital inpatients in non-endemic We have found evidence contrary to the majority areas. opinion. We studied 24 cases of acute falciparum malaria first seen and admitted in a hospital in the endemic area. All were treated promptly with quinine. 6 were complicated by clinical jaundice, 2 had cerebral symptoms, and 1 developed fatal pulmonary oedema. The others recovered. SIR,-There
are
Parasite counts and platelet counts were made on admission. Fibrinogen levels were determined by radial immunodiffusion. Serum fibrinogen degradation products !F.D.P.) were determined according to Das,,’ and F.D.P. and fibrinogen values on the third day after admission were available in 16 cases. In 8 cases there was a slight increase in serum-F.D.P. (above 10 tLg. per ml.) and hypofibrinogenmmia (below 200 mg. per 100 ml.), singly or together. In these 8 cases, all except 1 had heavy parasitaEmia above 100,000 per c.mm. and clinical complications. Those which did not have increased intravascular coagulation were 2 patients with cerebral malaria, 1 with jaundice, and 1 with no complications and a parasite count above 100,000 per c.mm. Thrombocytopenia was found in 23 cases. Thrombocytopenia in malaria could be caused by other mechanismsand it should not be taken as evidence of intravascular coagulation. Highest serum-F.D.p. levels in these patients are still much lower than the value found in classical disseminated intravascular coagulation. In our patients a mildly increased intravascular coagulation could be detected in a third and it was associated closely with heavy parasitoemia.
Our conclusion is that increased intravascular
cbagula-
Reid, H. A., Nkrumah, R. K. Lancet, 1972, i, 218. Jaroonvesama, N. ibid. p. 221. 3. Neva, F. A., Sheagren, J. N., Shulman, N. R., Canfield, C. J. Ann. intern Med. 1970, 73, 295. 4. Punyagupta, S., Srichaikul, R., Nitiyanant, P., Petchclai, B. Am. J. trop. Med. Hyg. 1974, 23, 551. 5. Das, P. C. J. clin. Path. 1970, 23, 299.
1. 2.
BENCHA PETCHCLAI SOPAPORN PRASONGSOM WISITH BENJAPONGS.
ANTICOAGULANT CONTROL, IMMUNOSUPPRESSION, AND GLOMERULONEPHRITIS
SIR,-In a paper (Nov. 16, p. 1166) on anticoagulant immunosuppressant treatment of rapidly progressive glomerulonephritis, the data on the degree of anticoagula-
and
tion and its control
were
incorrect.
coagulant regimen was carried hoematology, as follows:
out
Control of the antiin the department of
Heparin therapy was controlled on the kaolin-cephalin time (K.C.T.). The patients injected their heparin subcutaneously into the anterior abdominal wall, the doses varying between 6000 and 15,000 units 8-hourly, and blood-samples for the K.C.T. were taken 3-4 hours after the last injection. The K.C.T. was prolonged for 60-100 seconds (normal control 30-35 seconds). The K.C.T. was preferred to the thrombin-time, after trial, because of its better reproducibility. At aK.C.T. of 60-100 seconds the corresponding thrombin-times were prolonged 5-fold or more above the control time of 11-14 seconds and the end-points were very poor. Warfarin therapy was controlled by the one-stage prothrombintime using human brain thromboplastin (Manchester Comparative Reagent), the normal control times being 12-13 seconds and the therapeutic range 30-50 seconds. This therapeutic range corresponds to a prothrombin concentration of 15-5%, as determined from a dilution curve prepared from normal plasma diluted with barium-sulphate-absorbed normal plasma. This range has been in use for some years at Guy’s for all patients on oral anticoagulant therapy. "
"
The level of anticoagulation was, in greater than was implied in the paper.
Department of Hæmatology, Renal
Unit, Guy’s Hospital, London SE1 9RT.
general, somewhat P. BARKHAN P. J. BLACK T. THOMAS. C. B. BROWN
J. S. CAMERON C. S. OGG.
CALCIUM BALANCE IN PREGNANCY
SIR,-Dr Hytten and his colleagues (Nov. 9, p. 1152) make several criticisms of our paper (Oct. 19, p. 926) on this subject. The references used to support their contention that metabolic balance studies are of little value 1,2 do not take into account the use of faecal markers and do not fulfil the requirements set down by later workers,3,4 especially regarding previous dietary histories and the importance Our studies of subjects continuing on the same diet, &c. fulfilled these criteria and, as the agreement between results in the two balance periods was good, then stabilisation of the subject has almost certainly occurred. We do not recommend a calcium intake of 2 g. per day, but suggest that our results on the 7 subjects we studied indicate that this amount may be necessary for calcium balance. Further studies are obviously required. Radiological studies are notoriously unreliable in establishing loss of bone calcium since the loss has to be considerable before any change can be detected. Finally, the biochemical results in plasma and urine in 1. 2. 3. 4.
Duncan, D. Forbes, G. Hargreaves, Hartley, T. 1974, 52,
L. Nutr. Abstr. Rev. 1958, 28, 695. Nutr. Rev. 1973, 31, 297. T., Rose, G. A. Clin. Sci. 1965, 28, 537. F., Dawson, J. B., Hodgkinson, A. Clinica chim. Acta, 321.
The non-invasive diagnosis of the Zollinger-Ellison syndrome hinges on the secretin test: a marked rise in a serum-gastrin, which is almost all big " gastrin, is very suggestive of a tumour. This test does require further evaluation before its routine use can be accepted. The therapeutic effect of metiamide in this case was dramatic, suggesting a major therapeutic role for metiamide in patients with refractory peptic ulceration, and possibly in the Zollinger-Ellison syndrome. We are at a loss to explain the striking changes in the fasting serum-gastrin during therapy, but they were greater than any of the day-to-day variations we have seen in this patient. Another two similar patients have been treated with
not contribute to cerebral symptoms and it is serious problem in acute falciparum malarias treated adequately in the endemic area.
tion does not a
Ramathibodi
Hospital, Bangkok 4, and Phrabudhabat Hospital, Saraburi, Thailand.
"
metiamide over a shorter period. The initial response assessed symptomatically and endoscopically was as good as in the above patient. Department of Surgery, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 4LP. Sunderland Royal Infirmary, Sunderland, Co. Durham.
Department of Physiology, University of Newcastle upon Tyne.
M. H. THOMPSON C. W. VENABLES. I. T. J. D. D. J. E. R. E. L.
MILLER.
REED SANDERS GRUND BLAIR.
INTRAVASCULAR COAGULATION AND MALARIA
conflicting reports 14 of the incidence of increased intravascular coagulation in malaria. Most reports of increased intravascular coagulation came from selected groups of hospital inpatients in non-endemic We have found evidence contrary to the majority areas. opinion. We studied 24 cases of acute falciparum malaria first seen and admitted in a hospital in the endemic area. All were treated promptly with quinine. 6 were complicated by clinical jaundice, 2 had cerebral symptoms, and 1 developed fatal pulmonary oedema. The others recovered. SIR,-There
are
Parasite counts and platelet counts were made on admission. Fibrinogen levels were determined by radial immunodiffusion. Serum fibrinogen degradation products !F.D.P.) were determined according to Das,,’ and F.D.P. and fibrinogen values on the third day after admission were available in 16 cases. In 8 cases there was a slight increase in serum-F.D.P. (above 10 tLg. per ml.) and hypofibrinogenmmia (below 200 mg. per 100 ml.), singly or together. In these 8 cases, all except 1 had heavy parasitaEmia above 100,000 per c.mm. and clinical complications. Those which did not have increased intravascular coagulation were 2 patients with cerebral malaria, 1 with jaundice, and 1 with no complications and a parasite count above 100,000 per c.mm. Thrombocytopenia was found in 23 cases. Thrombocytopenia in malaria could be caused by other mechanismsand it should not be taken as evidence of intravascular coagulation. Highest serum-F.D.p. levels in these patients are still much lower than the value found in classical disseminated intravascular coagulation. In our patients a mildly increased intravascular coagulation could be detected in a third and it was associated closely with heavy parasitoemia.
Our conclusion is that increased intravascular
cbagula-
Reid, H. A., Nkrumah, R. K. Lancet, 1972, i, 218. Jaroonvesama, N. ibid. p. 221. 3. Neva, F. A., Sheagren, J. N., Shulman, N. R., Canfield, C. J. Ann. intern Med. 1970, 73, 295. 4. Punyagupta, S., Srichaikul, R., Nitiyanant, P., Petchclai, B. Am. J. trop. Med. Hyg. 1974, 23, 551. 5. Das, P. C. J. clin. Path. 1970, 23, 299.
1. 2.
BENCHA PETCHCLAI SOPAPORN PRASONGSOM WISITH BENJAPONGS.
ANTICOAGULANT CONTROL, IMMUNOSUPPRESSION, AND GLOMERULONEPHRITIS
SIR,-In a paper (Nov. 16, p. 1166) on anticoagulant immunosuppressant treatment of rapidly progressive glomerulonephritis, the data on the degree of anticoagula-
and
tion and its control
were
incorrect.
coagulant regimen was carried hoematology, as follows:
out
Control of the antiin the department of
Heparin therapy was controlled on the kaolin-cephalin time (K.C.T.). The patients injected their heparin subcutaneously into the anterior abdominal wall, the doses varying between 6000 and 15,000 units 8-hourly, and blood-samples for the K.C.T. were taken 3-4 hours after the last injection. The K.C.T. was prolonged for 60-100 seconds (normal control 30-35 seconds). The K.C.T. was preferred to the thrombin-time, after trial, because of its better reproducibility. At aK.C.T. of 60-100 seconds the corresponding thrombin-times were prolonged 5-fold or more above the control time of 11-14 seconds and the end-points were very poor. Warfarin therapy was controlled by the one-stage prothrombintime using human brain thromboplastin (Manchester Comparative Reagent), the normal control times being 12-13 seconds and the therapeutic range 30-50 seconds. This therapeutic range corresponds to a prothrombin concentration of 15-5%, as determined from a dilution curve prepared from normal plasma diluted with barium-sulphate-absorbed normal plasma. This range has been in use for some years at Guy’s for all patients on oral anticoagulant therapy. "
"
The level of anticoagulation was, in greater than was implied in the paper.
Department of Hæmatology, Renal
Unit, Guy’s Hospital, London SE1 9RT.
general, somewhat P. BARKHAN P. J. BLACK T. THOMAS. C. B. BROWN
J. S. CAMERON C. S. OGG.
CALCIUM BALANCE IN PREGNANCY
SIR,-Dr Hytten and his colleagues (Nov. 9, p. 1152) make several criticisms of our paper (Oct. 19, p. 926) on this subject. The references used to support their contention that metabolic balance studies are of little value 1,2 do not take into account the use of faecal markers and do not fulfil the requirements set down by later workers,3,4 especially regarding previous dietary histories and the importance Our studies of subjects continuing on the same diet, &c. fulfilled these criteria and, as the agreement between results in the two balance periods was good, then stabilisation of the subject has almost certainly occurred. We do not recommend a calcium intake of 2 g. per day, but suggest that our results on the 7 subjects we studied indicate that this amount may be necessary for calcium balance. Further studies are obviously required. Radiological studies are notoriously unreliable in establishing loss of bone calcium since the loss has to be considerable before any change can be detected. Finally, the biochemical results in plasma and urine in 1. 2. 3. 4.
Duncan, D. Forbes, G. Hargreaves, Hartley, T. 1974, 52,
L. Nutr. Abstr. Rev. 1958, 28, 695. Nutr. Rev. 1973, 31, 297. T., Rose, G. A. Clin. Sci. 1965, 28, 537. F., Dawson, J. B., Hodgkinson, A. Clinica chim. Acta, 321.
