977
Since HCV-Ab tests were introduced, all donor panels have been screened, and the incidence of HCV-Ab positivity has predictably
fallen in donors who donate repeatedly. Equally, the fractionation industry has improved its virus inactivation processes: the plasma products reflect both improvements in increased safety. The debate that should be pursued by ABRA and others is about the prevalence of transmittable disease in the blood of populations who donate freely as opposed to those donating for money. Central Blood Laboratories Authority, Elstree, Herts WD6 3AU, UK
JL, et al. Detection of antibodies to hepatitis C virus in US blood donors. J Clin Microbiol 1991; 29: 551. Ortho HCV ELISA Test 2. Hepatitis C virus encoded antigen (recombinant < 100-3). System Package Insert.
Rodell is apparently still not convinced that a non-remunerated blood donor scheme can produce national self-sufficiency in blood and blood products. If it is possible to do this in countries such as New Zealandl and Australia, surely it should be possible to do it elsewhere? Although it does need a close and intelligent cooperation between government authorities and the blood services, as well as the appropriate legislation to prevent buying and selling of blood, the goal of blood and blood product self-sufficiency is not only feasible but also attainable. A remunerated blood donor system nearly always leads to a variety of problems. Blood and money, like oil and water, do not mix well. Department of Transfusion Medicine, Regional Blood Services,
Auckland
1. Woodfield DG. National self
Zealand experience.
sufficiency in blood and Transfusion Today 1990, 7: 3-4.
D. G. WOODFIELD blood
products:
the New
Can you make a bottle? brings new stress to life. Working in a gastroenterology specialist unit, I find the association1 between bottle feeding and gastroenteritis to be obvious. My experience of paternal stress was trying to learn how to make up properly a bottle of infant formula. Having mastered the technique, I wondered if my colleagues would know how I managed to complete this task. I therefore questioned 8 doctors in the unit (1professor, 1 consultant, 2 lecturers, 2 research fellows, and 2 junior doctors). I asked: (1) How long should you boil a bottle for, to ensure it is sterile? (Answer, 10 min.) (2) If you submerge the bottle in Milton, how long before it is sterile? (30 min.) (3) What type of water should you use? (Boiled.) (4) At what temperature should this water be? (Tepid, (5) How long can you keep a bottle refrigerated before it should be discarded? (24 h.) The average of correct answers was only 2, and none answered all 5 correctly. Before my own practical experience my knowledge would have been similarly scant. I am now able to find out during my history taking if there is a difficulty with the sterilisation technique used by a parent of a child with gastroenteritis. If you are a doctor who treats children with gastroenteritis you should ask youself: can I make up a bottle? Paediatric Gastroenterology, Queen Elizabeth Hospital for Children, London E2 8PS, UK 1.
Office of International Cooperation, World Health Organization, 1211 Geneva, Switzerland
MICHEL JANCLOES
RICHARD S. LANE
1. Dawson GJ, Lesniewski RR, Stewart
Grafton, Auckland, New Zealand
Director-General. Furthermore, the close working relations in the field and co-ordination of policies that exist between WHO and the World Bank continuously enrich the reciprocal awareness of both institutions of the issue. How can such shared experience leave the World Bank oblivious to the wider health aspects of its policies?
Deputy
P. JONES
Walker-Smith J. Disease of the small intestine of children. 3rd ed, 1988: 20.
Quality of economy comment (July 11, p 110) on an important event organised by WHO last June. However, I would draw to your attention errors in the statements attributed to both the Deputy Director-General of WHO and myself, which have given rise to misinterpretations. There was no mention of a "hydro-electric plant" in the opening speech by the
Treatment of hypophosphataemia draw your attention to what may be a potentially hazardous dose of phosphate recommended for the treatment of hypophosphataemia in the British National Formulary (BNF). A solution containing up to 50 mmol/1 in sodium chloride or glucose is advised by intravenous infusion over 12-24 h.l The dangers of excessive phosphate infusion are hypocalcaemia and metastatic calcification due to the formation of calcium phosphate salts. Accordingly Vannatta et described a regimen of 9 mmol/1 monobasic potassium hydrogen phosphate given over 12 h for the treatment of severe hypophosphataemia ( < 0-32 mmol/1). In ten patients thus treated, only one had a slight drop in serum total calcium. This protocol was subsequently supported by you in 1981.3 However, even with this protocol, we have found that plasma ionised calcium may fall to very low levels (to 0-72 mmol/1, reference Although our patients remained symptom-free, the potential for severe hypocalcaemia is evident and we would recommend adhering to the Vannatta regimenz while measuring ionised calcium, phosphate, and potassium every 6 hours. We have informed the BNF of our findings and the dosage of intravenous phosphate for the treatment of hypophosphataemia is being discussed by their Joint Formulary Committee for revision of the text. Departments of Chemical Pathology and Haematology, St James’s University Hospital, Leeds LS9 7TF, UK
S. COYLE P. W. MASTERS D. BARNARD
1. British National Formulary. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 1992; 23: 337. 2. Vannatta JB, Whang R, Papper S. Efficacy of intravenous phosphate therapy in the severely hypophosphataemic patient. Arch Intern Med 1981; 141: 885-87. 3. Anon. Treatment of severe hypophosphataemia. Lancet 1981, ii: 734. 4. Coyle S, Masters PW, Barnard D. TmP/GFR and ionized calcium in the management of severe hypophosphataemia. Ann Clin Biochem 1992; 29: 567-69.
Vincristine for thrombotic purpura O’Connor and colleagues’ report (Aug 22, p 490) that
thrombocytopenic
vincristine
is
effective
in
the
treatment
of
thrombotic
thrombocytopenic purpura (TTP) and should be given at the time of diagnosis. Because in their patients this drug had been given with fresh frozen plasma or other treatments, they should have provided more detail on combined therapies. Was fresh frozen plasma given by plasmapheresis or by simple infusion? Simple infusion has proved less effective than plasma exchange.1 About 80 patients reviewed in published work had received vincristine for TTP, but the drug has usually been used with other treatments and it is difficult to deduce which treatment was most responsible for the improvement.2-4 Our experience, however, confirms that vincristine is useful in TTP, but we do not think that vincristine is adequate as a single agent in patients with severe TTP (severity score ranging from 5 to 8).5 Severe disease needs the rapid improvement that can happen only after plasma exchange. However, the remission seen after plasmapheresis is often transient, and vincristine seems useful for the prevention of relapses and shortening of duration of disease. We have previously reported a patient with severe TTP, refractory to intensive plasma exchange and antiplatelet agents, who responded strikingly after vincristine.4 We have now treated prospectively 6 patients with severe TTP (platelets under 20 x 109/ 1, haemoglobin under 8 g/dl, and neurological dysfunction) with
978
vincristine in addition to plasma exchange and anti-platelet agents. was done daily for 5 days and then two or three times per week until patients achieved complete remission. In 4 patients, vincristine was given at the time of diagnosis. In all patients platelet count increased to above 100 x 109/1, within 5 days but improvement was transient, and subsequent injections of vincristine were given (total dose ranging from 4 to 8 mg). In the 2 patients who received vincristine during the course of the disease, plasma exchange seemed less effective. 1 patient with severe neurological impairment died despite aggressive therapy. However, he died only a few days after presentation, probably as a result of fulminant TTP rather than the absence of initial vincristine therapy. In the other patient, time to maximum response and disease remission was delayed. Response was achieved only when vincristine was added to plasma exchange. Vincristine is potentially toxic and we do not think that a 2 mg bolus followed by two further injections on alternate days is a realistic schedule. Furthermore, in severe TTP, plasma exchange remains more effective as first-line treatment.’ We recommend a first 2 mg injection in combination with daily plasma exchange, followed by a second bolus 5 days later, then 1 mg every week dependent on platelet counts and other features of the disease. Since initial treatment with weekly vincristine concomitant with plasmapheresis on a daily schedule results in rapid improvement in platelet count and decreased morbidity and mortality, we agree that prospective studies of vincristine alone should be compared with plasma exchange, especially in patients with a low severity score.
Plasmapheresis
Department of Internal Medicine, Hôpital Sainte-Marguerite, 13274 Marseille, France; and Department of Haemobiology,
Hôpital de
al
Conception, Marseille
JEAN MARC DURAND PATRICE LEFEVRE GILLES KAPLANSKI HELENE TELLE JACQUES SOUBEYRAND
1. Rock
Frequency of NFTs and SPs among leprosy and non-leprosy subjects aged over 70 years.
2.
H=hippocampus, P=parahippocampal temporal gyrus. NS= not significant,* p 70
years). We found NFTs in varying amounts in hippocampus, gyrus, and occipitotemporal gyrus in leprosy patients. There was no significant difference in the frequency between our data and the standard data (figure). By contrast, we
parahippocampal
The absence of SPs in the hippocampal, parahippocampal, and occipitotemporal regions in elderly, non-demented leprosy patients was surprising, in view of the similar occurrence ofNFTs in the two groups of elderly subjects. Mycobacterium leprae infection and/or continuous or intermittent use of anti-inflammatory drugs may be relevant. Although the lack of SPs itself is not necessarily correlated with the supposed low prevalence of dementia in leprosy patients, our results may help in the clarification of the pathogenesis of SPs. Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, Setagayaku, Tokyo 156, Japan, Department of Microbiology and Bioregulation, National Institute for Leprosy Research, Tokyo, Japan, Department of Neuropathology, Institute of Brain Research, University of Tokyo, and Department of Neurology, Jichi Medical School,
Omiya, Japan 1.
YOSHIO NAMBA KUNIO KAWATSU SHINZO IZUMI AKIRA UEKI KAZUHIKO IKEDA
McGeer PL, Harada N, Kimura H, McGeer EG, Schulzer M Prevalence of dementia amongst elderly Japanese with leprosy: apparent effect of chronic drug therapy. Dementia 1992; 3: 146-49.
2. Ihara Y. Massive somatodendritic sprouting of cortical neurons in Alzheimer’s disease. Brain Res 1988; 459: 138-44. 3. Allsop D, Landon M, Kidd M, Lowe JS, Reynold GP, Gardner A. Monoclonal
against a subsequence of senile plaque core protein react with plaque core, plaque periphery and cerebrovascular amyloid in Alzheimer’s disease. Neurosci Lett 1986; 68: 252-56. 4. Kuzuhara S, Ihara Y, Shimada H, Toyokura Y. &bgr;-protein and tau immunohistochemistry on brains of normal aging and dementia. In: Ishii T, Allsop D, Selkoe DJ, eds. Frontiers of Alzheimer research. Amsterdam: Excerpta Medica, antibodies raised
1991: 87-97.
Since HCV-Ab tests were introduced, all donor panels have been screened, and the incidence of HCV-Ab positivity has predictably
fallen in donors who donate repeatedly. Equally, the fractionation industry has improved its virus inactivation processes: the plasma products reflect both improvements in increased safety. The debate that should be pursued by ABRA and others is about the prevalence of transmittable disease in the blood of populations who donate freely as opposed to those donating for money. Central Blood Laboratories Authority, Elstree, Herts WD6 3AU, UK
JL, et al. Detection of antibodies to hepatitis C virus in US blood donors. J Clin Microbiol 1991; 29: 551. Ortho HCV ELISA Test 2. Hepatitis C virus encoded antigen (recombinant < 100-3). System Package Insert.
Rodell is apparently still not convinced that a non-remunerated blood donor scheme can produce national self-sufficiency in blood and blood products. If it is possible to do this in countries such as New Zealandl and Australia, surely it should be possible to do it elsewhere? Although it does need a close and intelligent cooperation between government authorities and the blood services, as well as the appropriate legislation to prevent buying and selling of blood, the goal of blood and blood product self-sufficiency is not only feasible but also attainable. A remunerated blood donor system nearly always leads to a variety of problems. Blood and money, like oil and water, do not mix well. Department of Transfusion Medicine, Regional Blood Services,
Auckland
1. Woodfield DG. National self
Zealand experience.
sufficiency in blood and Transfusion Today 1990, 7: 3-4.
D. G. WOODFIELD blood
products:
the New
Can you make a bottle? brings new stress to life. Working in a gastroenterology specialist unit, I find the association1 between bottle feeding and gastroenteritis to be obvious. My experience of paternal stress was trying to learn how to make up properly a bottle of infant formula. Having mastered the technique, I wondered if my colleagues would know how I managed to complete this task. I therefore questioned 8 doctors in the unit (1professor, 1 consultant, 2 lecturers, 2 research fellows, and 2 junior doctors). I asked: (1) How long should you boil a bottle for, to ensure it is sterile? (Answer, 10 min.) (2) If you submerge the bottle in Milton, how long before it is sterile? (30 min.) (3) What type of water should you use? (Boiled.) (4) At what temperature should this water be? (Tepid, (5) How long can you keep a bottle refrigerated before it should be discarded? (24 h.) The average of correct answers was only 2, and none answered all 5 correctly. Before my own practical experience my knowledge would have been similarly scant. I am now able to find out during my history taking if there is a difficulty with the sterilisation technique used by a parent of a child with gastroenteritis. If you are a doctor who treats children with gastroenteritis you should ask youself: can I make up a bottle? Paediatric Gastroenterology, Queen Elizabeth Hospital for Children, London E2 8PS, UK 1.
Office of International Cooperation, World Health Organization, 1211 Geneva, Switzerland
MICHEL JANCLOES
RICHARD S. LANE
1. Dawson GJ, Lesniewski RR, Stewart
Grafton, Auckland, New Zealand
Director-General. Furthermore, the close working relations in the field and co-ordination of policies that exist between WHO and the World Bank continuously enrich the reciprocal awareness of both institutions of the issue. How can such shared experience leave the World Bank oblivious to the wider health aspects of its policies?
Deputy
P. JONES
Walker-Smith J. Disease of the small intestine of children. 3rd ed, 1988: 20.
Quality of economy comment (July 11, p 110) on an important event organised by WHO last June. However, I would draw to your attention errors in the statements attributed to both the Deputy Director-General of WHO and myself, which have given rise to misinterpretations. There was no mention of a "hydro-electric plant" in the opening speech by the
Treatment of hypophosphataemia draw your attention to what may be a potentially hazardous dose of phosphate recommended for the treatment of hypophosphataemia in the British National Formulary (BNF). A solution containing up to 50 mmol/1 in sodium chloride or glucose is advised by intravenous infusion over 12-24 h.l The dangers of excessive phosphate infusion are hypocalcaemia and metastatic calcification due to the formation of calcium phosphate salts. Accordingly Vannatta et described a regimen of 9 mmol/1 monobasic potassium hydrogen phosphate given over 12 h for the treatment of severe hypophosphataemia ( < 0-32 mmol/1). In ten patients thus treated, only one had a slight drop in serum total calcium. This protocol was subsequently supported by you in 1981.3 However, even with this protocol, we have found that plasma ionised calcium may fall to very low levels (to 0-72 mmol/1, reference Although our patients remained symptom-free, the potential for severe hypocalcaemia is evident and we would recommend adhering to the Vannatta regimenz while measuring ionised calcium, phosphate, and potassium every 6 hours. We have informed the BNF of our findings and the dosage of intravenous phosphate for the treatment of hypophosphataemia is being discussed by their Joint Formulary Committee for revision of the text. Departments of Chemical Pathology and Haematology, St James’s University Hospital, Leeds LS9 7TF, UK
S. COYLE P. W. MASTERS D. BARNARD
1. British National Formulary. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 1992; 23: 337. 2. Vannatta JB, Whang R, Papper S. Efficacy of intravenous phosphate therapy in the severely hypophosphataemic patient. Arch Intern Med 1981; 141: 885-87. 3. Anon. Treatment of severe hypophosphataemia. Lancet 1981, ii: 734. 4. Coyle S, Masters PW, Barnard D. TmP/GFR and ionized calcium in the management of severe hypophosphataemia. Ann Clin Biochem 1992; 29: 567-69.
Vincristine for thrombotic purpura O’Connor and colleagues’ report (Aug 22, p 490) that
thrombocytopenic
vincristine
is
effective
in
the
treatment
of
thrombotic
thrombocytopenic purpura (TTP) and should be given at the time of diagnosis. Because in their patients this drug had been given with fresh frozen plasma or other treatments, they should have provided more detail on combined therapies. Was fresh frozen plasma given by plasmapheresis or by simple infusion? Simple infusion has proved less effective than plasma exchange.1 About 80 patients reviewed in published work had received vincristine for TTP, but the drug has usually been used with other treatments and it is difficult to deduce which treatment was most responsible for the improvement.2-4 Our experience, however, confirms that vincristine is useful in TTP, but we do not think that vincristine is adequate as a single agent in patients with severe TTP (severity score ranging from 5 to 8).5 Severe disease needs the rapid improvement that can happen only after plasma exchange. However, the remission seen after plasmapheresis is often transient, and vincristine seems useful for the prevention of relapses and shortening of duration of disease. We have previously reported a patient with severe TTP, refractory to intensive plasma exchange and antiplatelet agents, who responded strikingly after vincristine.4 We have now treated prospectively 6 patients with severe TTP (platelets under 20 x 109/ 1, haemoglobin under 8 g/dl, and neurological dysfunction) with
978
vincristine in addition to plasma exchange and anti-platelet agents. was done daily for 5 days and then two or three times per week until patients achieved complete remission. In 4 patients, vincristine was given at the time of diagnosis. In all patients platelet count increased to above 100 x 109/1, within 5 days but improvement was transient, and subsequent injections of vincristine were given (total dose ranging from 4 to 8 mg). In the 2 patients who received vincristine during the course of the disease, plasma exchange seemed less effective. 1 patient with severe neurological impairment died despite aggressive therapy. However, he died only a few days after presentation, probably as a result of fulminant TTP rather than the absence of initial vincristine therapy. In the other patient, time to maximum response and disease remission was delayed. Response was achieved only when vincristine was added to plasma exchange. Vincristine is potentially toxic and we do not think that a 2 mg bolus followed by two further injections on alternate days is a realistic schedule. Furthermore, in severe TTP, plasma exchange remains more effective as first-line treatment.’ We recommend a first 2 mg injection in combination with daily plasma exchange, followed by a second bolus 5 days later, then 1 mg every week dependent on platelet counts and other features of the disease. Since initial treatment with weekly vincristine concomitant with plasmapheresis on a daily schedule results in rapid improvement in platelet count and decreased morbidity and mortality, we agree that prospective studies of vincristine alone should be compared with plasma exchange, especially in patients with a low severity score.
Plasmapheresis
Department of Internal Medicine, Hôpital Sainte-Marguerite, 13274 Marseille, France; and Department of Haemobiology,
Hôpital de
al
Conception, Marseille
JEAN MARC DURAND PATRICE LEFEVRE GILLES KAPLANSKI HELENE TELLE JACQUES SOUBEYRAND
1. Rock
Frequency of NFTs and SPs among leprosy and non-leprosy subjects aged over 70 years.
2.
H=hippocampus, P=parahippocampal temporal gyrus. NS= not significant,* p 70
years). We found NFTs in varying amounts in hippocampus, gyrus, and occipitotemporal gyrus in leprosy patients. There was no significant difference in the frequency between our data and the standard data (figure). By contrast, we
parahippocampal
The absence of SPs in the hippocampal, parahippocampal, and occipitotemporal regions in elderly, non-demented leprosy patients was surprising, in view of the similar occurrence ofNFTs in the two groups of elderly subjects. Mycobacterium leprae infection and/or continuous or intermittent use of anti-inflammatory drugs may be relevant. Although the lack of SPs itself is not necessarily correlated with the supposed low prevalence of dementia in leprosy patients, our results may help in the clarification of the pathogenesis of SPs. Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, Setagayaku, Tokyo 156, Japan, Department of Microbiology and Bioregulation, National Institute for Leprosy Research, Tokyo, Japan, Department of Neuropathology, Institute of Brain Research, University of Tokyo, and Department of Neurology, Jichi Medical School,
Omiya, Japan 1.
YOSHIO NAMBA KUNIO KAWATSU SHINZO IZUMI AKIRA UEKI KAZUHIKO IKEDA
McGeer PL, Harada N, Kimura H, McGeer EG, Schulzer M Prevalence of dementia amongst elderly Japanese with leprosy: apparent effect of chronic drug therapy. Dementia 1992; 3: 146-49.
2. Ihara Y. Massive somatodendritic sprouting of cortical neurons in Alzheimer’s disease. Brain Res 1988; 459: 138-44. 3. Allsop D, Landon M, Kidd M, Lowe JS, Reynold GP, Gardner A. Monoclonal
against a subsequence of senile plaque core protein react with plaque core, plaque periphery and cerebrovascular amyloid in Alzheimer’s disease. Neurosci Lett 1986; 68: 252-56. 4. Kuzuhara S, Ihara Y, Shimada H, Toyokura Y. &bgr;-protein and tau immunohistochemistry on brains of normal aging and dementia. In: Ishii T, Allsop D, Selkoe DJ, eds. Frontiers of Alzheimer research. Amsterdam: Excerpta Medica, antibodies raised
1991: 87-97.
