- Email: [email protected]
Trading trust for blood money
these communities. Intervention trials are generally of most if they address a single well-defined question. Our trial was designed specifically to test the impact of improved STD treatment on HIV incidence, and this is what it achieved. Had sexual behaviour also changed in the intervention group, there would be no way of knowing whether improving STD treatment had any effect at all. Clearly our study provides no information on the effectiveness of programmes aimed mainly at behaviour change, and it is remarkable, so far into the epidemic, that no randomised trials have been undertaken to address this issue. We repeat the view expressed in our report that AIDS control programmes need to combine effective behavioural interventions with improved STD treatment services to yield maximum impact on the spread of HIV. Adequate public health services for the diagnosis and treatment of STDs should be regarded as a basic right, and not as a "magic bullet". use
Richard
Hayes, *Heiner Grosskurth, Gina ka-Gina
*Tropical Health Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK; and AMREF, Mwanza, Tanzania
1
2
Changalucha J, Grosskurth H, et al. Antimicrobial susceptibility, auxotype and plasmid content of Neisseria gonorrhoeae in Northern Tanzania: emergence of high level plasmid mediated tetracycline resistance. Genitourin Med 1995; 71: 9-12. Senn S. Testing for baseline balance in clinical trials. Stat Med 1994; West B,
13: 1715-26.
cerebrovascular disease were included, in addition to coronary artery disease. Diabetic nephropathy was either biopsy proven or defined as the presence of persistent proteinuria (>500 mg per 24 h) with associated hypertension and diabetic retinopathy, with no evidence of other renal diseases. The PCR conditions and restriction endonuclease used were similar to those of Katsuya. The table shows our results. We showed no relation between the genotypes of the T235 polymorphism and the presence of hypertension, macrovascular disease, or microvascular disease, with the X2 test for statistical analysis. Controlling for sex, smoking habit, and hypertension did not alter the results. Similarly, increased risk of developing vascular disease or nephropathy was not associated with the presence of the T allele (relative risks 0-86 and 1-18, respectively). The hypothesis that there is a role for the genetic determinants of renin-angiotensin system activity in macrovascular and microvascular disease progression is attractive. Ideally, to investigate fully the possible effects that genetic polymorphisms may have on disease progression, should several studies evaluate candidate genes to their and, credit, simultaneously2 Katsuya and colleagues have tried to address this issue. The clinical importance of candidate genes needs to be evaluated by prospective trials before screening can be advocated. *K J
1
Effect of angiotensinogen gene T235 variant on the development of diabetic complications in type II diabetes mellitus SiR-Katsuya and colleagues (June 24, p 1600) report an increased risk of coronary heart disease in individuals who are homozygous for the T235 polymorphism of the angiotensinogen gene. These findings are open to at least two interpretations. On the one hand, they provide further evidence of a role for genetic factors influencing the activity of the renin-angiotensin system in the development of this condition. Conversely, the apparent innocence of the insertion/deletion polymorphism of the ACE gene and C1166 polymorphism of the 47 receptor gene in coronary artery disease and the T235 polymorphism in hypertension are potentially contradictory to previous studies and should be viewed as negative results. We have investigated the effect of the T235 polymorphism of the angiotensinogen gene in the development of microvascular and macrovascular complications in 44 male and 32 female patients with type II diabetes. Definition of macrovascular disease was similar to that of Katsuya-ie, by a history of a documented ischaemic event or proven by investigation. Peripheral vascular disease and
*BP
(blood pressure) >160/95 mm Hg, or receiving antihypertensive treatment. Table: Genotype frequency of the T235 polymorphism of the angiotensinogen gene in individuals with or without diabetic
complications 1160
McLaughlin, C Jagger, M Small, A G Jardine
Renal Unit, Stobhill Hospital,
2
Glasgow G21 3UW, UK
Russ AP, Maerz W, Ruzicka V, Stein U, Gross W. Rapid detection of the hypertension-associated Met235→Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993; 2: 609-10. Tiret L, Bonnardequx A, Poirer O, et al. Synergistic effect of angiotensin-converting enzyme and angiotensin-II type I receptor polymorphisms on risk of myocardial infarction. Lancet 1994; 344: 910-13.
Trading trust for blood money SIR-I was angered and disappointed by your views and insinuations in your Sept 30 editorial. The facts are, first, that organisations have written to the National Blood Authority (NBA) suggesting ways in which they could become involved in our 50th anniversary celebrations in 1996. Second, The NBA did circulate these letters to certain key staff in advance of a forthcoming meeting. The covering note from the NBA asked these staff to consider the contents with a view to future discussion. Third, the documents were leaked to the press. The covering note from the NBA did not state that we would never give access to our donor records; this is such a cornerstone of the blood service that it does not need to be said within the service. Obviously, internal correspondence between senior colleagues need not always spell out the basic tenets that underpin practice in medicine and the National Health Service, just in case the correspondence is leaked. I agree that "the media cannot be blamed for publicising what they interpret as impropriety", but they can be blamed if there is no impropriety and where a full and open explanation of events is given. You were one of many given an extensive briefing by the NBA after the story appeared in the press. Your editorial is riddled with insinuation. Phrases such as "efficient and cost-effective business", "filleted ... to tempt prospective private bidders", "a helping hand from the private sector", "dubious connections with industrial sponsors", seeking in my view to convey an image that bears no relation to the truth. The NBA is a health authority; the national blood service is not a business, it is, and will remain, an integral part of the NHS; the blood service is not to be privatised; and we do not have any dubious connections with industrial sponsors.
I make no apology for the efforts of the blood service to raise the awareness of the donating and non-donating public. I repeat, we will never prejudice donor confidence by releasing details of our donors or allow our contacts with donors to be used as vehicles for commercial promotional mail. What failed was not the blood service but certain individuals who will stop at nothing in their efforts to undermine the generally accepted proposals for reorganisation. In the long run it is they who may damage donor confidence with potentially disastrous consequences for the blood supply and therefore the NHS.
E Angela E Robinson National Blood Authority, Oak House, Watford, Herts
In 1972
of aplastic anaemia was treated with cord felt we had a transplant. HLA typing did again not change, and we wondered whether it was possible to have a red cell transplant without a white cell one. That patient died from miliary tuberculosis. All these patients came from my private practice and the work is summarised by my brother.’
1
UK
3
SiR-In your editorial you state in relation to donating blood that "In the USA, you do it for money". Not necessarily true. Proudly do I wear my 2-gallon-pin after having donated more than 7-6 L of my blood. Never have I been offered a single penny for this. Yes, a few cookies and a soft drink were given to us for free. Perhaps you thought of plasma donations, for which the donor indeed receives money in the USA. Claus A Pierach Abbott Northwestern Hospital, Minneapolis, MN 55407, USA
History of umbilical cord blood transplantation SIR—Wagner and colleagues (July 22, p 214)
state that "The of umbilical cord blood as a source of transplantable haemopoietic stem cells was first suggested in the early 1980s". That is incorrect. The idea of using cord blood for therapeutic purposes originated from me in Petersburg, Virginia, in the 1960s.’ You may argue that we were not successful in carrying out the transplantation but the idea was ours, and at least two of the authors of the Lancet article are aware of our 1972 paper. In the early 1960s I was giving cord blood randomly for advanced malignant disease to see if it would have any therapeutic effect.’ In 1964 cord blood was given to a patient with subacute lymphatic leukaemia whose haemoglobin was 5 g/dL. Haemoglobin, with no other therapy, rose to 10-8. After much discussion with my brother, Dr Norman Ende, we thought we had a transplant and set out to prove it. The obstetricians never took cord blood from the afterbirth until all cord pulsation had stopped. The above patient only received about 500 mL of cord blood. In 1966 a patient with myelogenous leukaemia was given around 500 mL of cord blood and we felt we had produced a transplant. Samples from the patient and the baby were sent to the Ortho Research Foundation, Raritan, New Jersey, for serological testing. The report on the patient’s red blood cells suggested that "the only surviving cells were those of the baby, and that we might not be detecting any of [the patient’s] blood. This does not seem feasible." In 1968 a patient with acute granulocytic leukaemia was given cord blood and again we felt we had a take. We found changes in the Fy’ and S factors, suggesting a transplant. The patient received chemotherapy. We did not publish this case because some of the blood used for testing antigens had haemolysed. The patient survived for more than 8 months, which was very unusual in such cases. In 1972 we published an article in Virginia Medical Monthly.2 This was a case of acute lymphoblastic leukaemia which by the means then available (HLA typing was in its infancy in 1970 when the patient was treated) proved we had a transplant. This patient lived for nearly a year after the graft, which again was most unusual. use
we
Milton Ende 121 S Market Street,
2
WD1 1QH,
a case
blood and
Petersburg,
VA
23803, USA
Ende U. Lymphangiosarcoma: report of a case. Pacific Med Surg 1966; 74: 80-82. Ende M, Ende N. Hematopoietic transplantation by means of fetal (cord) blood: a new method. Virginia Med Mon 1972; 99: 276. Ende N. Use of human umbilical cord blood for stem cell transplantation (HLA matched, unmatched; clinical; ethical, and legal aspects). In: Hematopoietic stem cells: biology and therapeutic applications. New York: Marcel Dekker, 1995.
Quality of chloroquine preparations marketed in Dar es Salaam, Tanzania SiR-Although chloroquine treatment failures in malaria are usually due to drug resistance, low compliance or the use of chloroquine preparations of poor quality could also be the reason. During screening tests for chloroquine intake we encountered a patient with a negative Haskins test even though she claimed to have taken chloroquine 2 days earlier. Since the sales of drugs of poor quality have been reported in Africa and elsewhere,1-4 we immediately suspected that the tablets she had taken were not genuine. Unfortunately, the patient did not have any tablets left. However, the incident prompted a small survey. One of us (GR) visited several pharmacy shops in Dar es Salaam and collected samples of chloroquine tablets of nine different brands marketed in the city. The tablets were properly stored and then sent to Sweden for quality control at the central laboratory of the National Corporation of Swedish Pharmacies, Stockholm (US Pharmacopeia, edition XXII). Tablets were tested for active ingredients and for dissolution rate. All brands complied with the USP requirements for amount of chloroquine (>97%). The eight brands of ordinary tablets also passed the dissolution test; the sugar-coated tablets did not (only 39% dissolved in 45 min, required minimum 75%). Drug dissolution is an important determinant of bioavailability. We do not know if this was the chloroquine preparation our patient took. In a recent study in Sudan one chloroquine brand manufactured locally had less than half the area under the plasma concentration curve of the imported brands5 and the preparation that did not comply with the dissolution test in our study was one produced locally in Tanzania. It would be of interest to explore this problem in other African countries that have local production capacity. *Yakoub Aden Abdi, Gerald Rimoy, Örjan Ericsson, Christina Alm, Amos Y Massele *Division of Clinical Pharmacology, Department of Medical Sciences and Technology, Karolinska Institute and Hospital Pharmacy, Huddinge University Hospital, S-14186 Huddinge, Sweden; and Department of Clinical Pharmacology, Muhimbili Medical Center, Dar Es Salaam, Tanzania
1
2 3 4 5
Murtada M, Sesay B. Expiry dates on pharmaceuticals—some worrying realities in Sierra Leone. Int Pharm J 1994; 8: 202-06. Abu-Reid IO, El-Samani SA, Hag Omer AI, et al. Stability of drugs in the tropics: a study in Sudan. Int Pharm J 1990; 4: 6-10. Dennis P, Edghill LA, Allen M, Acheampong YB. Quality control of pharmaceuticals in the Caribbean. Int Pharm J 1992; 6: 64-68. Kibwage IO, Ogeto JO, Maitai CK, et al. Drug quality control work in Daru: observations during 1983-1986. E Afr Med J 1992; 69: 577-80. Mahmoud BM, Ali HM, Homeida MMA, Bennett JL. Bioequivalence of five chloroquine brands marketed in Sudan. Int Pharm J 1994; 8: 164-67.
1161
Richard
Hayes, *Heiner Grosskurth, Gina ka-Gina
*Tropical Health Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK; and AMREF, Mwanza, Tanzania
1
2
Changalucha J, Grosskurth H, et al. Antimicrobial susceptibility, auxotype and plasmid content of Neisseria gonorrhoeae in Northern Tanzania: emergence of high level plasmid mediated tetracycline resistance. Genitourin Med 1995; 71: 9-12. Senn S. Testing for baseline balance in clinical trials. Stat Med 1994; West B,
13: 1715-26.
cerebrovascular disease were included, in addition to coronary artery disease. Diabetic nephropathy was either biopsy proven or defined as the presence of persistent proteinuria (>500 mg per 24 h) with associated hypertension and diabetic retinopathy, with no evidence of other renal diseases. The PCR conditions and restriction endonuclease used were similar to those of Katsuya. The table shows our results. We showed no relation between the genotypes of the T235 polymorphism and the presence of hypertension, macrovascular disease, or microvascular disease, with the X2 test for statistical analysis. Controlling for sex, smoking habit, and hypertension did not alter the results. Similarly, increased risk of developing vascular disease or nephropathy was not associated with the presence of the T allele (relative risks 0-86 and 1-18, respectively). The hypothesis that there is a role for the genetic determinants of renin-angiotensin system activity in macrovascular and microvascular disease progression is attractive. Ideally, to investigate fully the possible effects that genetic polymorphisms may have on disease progression, should several studies evaluate candidate genes to their and, credit, simultaneously2 Katsuya and colleagues have tried to address this issue. The clinical importance of candidate genes needs to be evaluated by prospective trials before screening can be advocated. *K J
1
Effect of angiotensinogen gene T235 variant on the development of diabetic complications in type II diabetes mellitus SiR-Katsuya and colleagues (June 24, p 1600) report an increased risk of coronary heart disease in individuals who are homozygous for the T235 polymorphism of the angiotensinogen gene. These findings are open to at least two interpretations. On the one hand, they provide further evidence of a role for genetic factors influencing the activity of the renin-angiotensin system in the development of this condition. Conversely, the apparent innocence of the insertion/deletion polymorphism of the ACE gene and C1166 polymorphism of the 47 receptor gene in coronary artery disease and the T235 polymorphism in hypertension are potentially contradictory to previous studies and should be viewed as negative results. We have investigated the effect of the T235 polymorphism of the angiotensinogen gene in the development of microvascular and macrovascular complications in 44 male and 32 female patients with type II diabetes. Definition of macrovascular disease was similar to that of Katsuya-ie, by a history of a documented ischaemic event or proven by investigation. Peripheral vascular disease and
*BP
(blood pressure) >160/95 mm Hg, or receiving antihypertensive treatment. Table: Genotype frequency of the T235 polymorphism of the angiotensinogen gene in individuals with or without diabetic
complications 1160
McLaughlin, C Jagger, M Small, A G Jardine
Renal Unit, Stobhill Hospital,
2
Glasgow G21 3UW, UK
Russ AP, Maerz W, Ruzicka V, Stein U, Gross W. Rapid detection of the hypertension-associated Met235→Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993; 2: 609-10. Tiret L, Bonnardequx A, Poirer O, et al. Synergistic effect of angiotensin-converting enzyme and angiotensin-II type I receptor polymorphisms on risk of myocardial infarction. Lancet 1994; 344: 910-13.
Trading trust for blood money SIR-I was angered and disappointed by your views and insinuations in your Sept 30 editorial. The facts are, first, that organisations have written to the National Blood Authority (NBA) suggesting ways in which they could become involved in our 50th anniversary celebrations in 1996. Second, The NBA did circulate these letters to certain key staff in advance of a forthcoming meeting. The covering note from the NBA asked these staff to consider the contents with a view to future discussion. Third, the documents were leaked to the press. The covering note from the NBA did not state that we would never give access to our donor records; this is such a cornerstone of the blood service that it does not need to be said within the service. Obviously, internal correspondence between senior colleagues need not always spell out the basic tenets that underpin practice in medicine and the National Health Service, just in case the correspondence is leaked. I agree that "the media cannot be blamed for publicising what they interpret as impropriety", but they can be blamed if there is no impropriety and where a full and open explanation of events is given. You were one of many given an extensive briefing by the NBA after the story appeared in the press. Your editorial is riddled with insinuation. Phrases such as "efficient and cost-effective business", "filleted ... to tempt prospective private bidders", "a helping hand from the private sector", "dubious connections with industrial sponsors", seeking in my view to convey an image that bears no relation to the truth. The NBA is a health authority; the national blood service is not a business, it is, and will remain, an integral part of the NHS; the blood service is not to be privatised; and we do not have any dubious connections with industrial sponsors.
I make no apology for the efforts of the blood service to raise the awareness of the donating and non-donating public. I repeat, we will never prejudice donor confidence by releasing details of our donors or allow our contacts with donors to be used as vehicles for commercial promotional mail. What failed was not the blood service but certain individuals who will stop at nothing in their efforts to undermine the generally accepted proposals for reorganisation. In the long run it is they who may damage donor confidence with potentially disastrous consequences for the blood supply and therefore the NHS.
E Angela E Robinson National Blood Authority, Oak House, Watford, Herts
In 1972
of aplastic anaemia was treated with cord felt we had a transplant. HLA typing did again not change, and we wondered whether it was possible to have a red cell transplant without a white cell one. That patient died from miliary tuberculosis. All these patients came from my private practice and the work is summarised by my brother.’
1
UK
3
SiR-In your editorial you state in relation to donating blood that "In the USA, you do it for money". Not necessarily true. Proudly do I wear my 2-gallon-pin after having donated more than 7-6 L of my blood. Never have I been offered a single penny for this. Yes, a few cookies and a soft drink were given to us for free. Perhaps you thought of plasma donations, for which the donor indeed receives money in the USA. Claus A Pierach Abbott Northwestern Hospital, Minneapolis, MN 55407, USA
History of umbilical cord blood transplantation SIR—Wagner and colleagues (July 22, p 214)
state that "The of umbilical cord blood as a source of transplantable haemopoietic stem cells was first suggested in the early 1980s". That is incorrect. The idea of using cord blood for therapeutic purposes originated from me in Petersburg, Virginia, in the 1960s.’ You may argue that we were not successful in carrying out the transplantation but the idea was ours, and at least two of the authors of the Lancet article are aware of our 1972 paper. In the early 1960s I was giving cord blood randomly for advanced malignant disease to see if it would have any therapeutic effect.’ In 1964 cord blood was given to a patient with subacute lymphatic leukaemia whose haemoglobin was 5 g/dL. Haemoglobin, with no other therapy, rose to 10-8. After much discussion with my brother, Dr Norman Ende, we thought we had a transplant and set out to prove it. The obstetricians never took cord blood from the afterbirth until all cord pulsation had stopped. The above patient only received about 500 mL of cord blood. In 1966 a patient with myelogenous leukaemia was given around 500 mL of cord blood and we felt we had produced a transplant. Samples from the patient and the baby were sent to the Ortho Research Foundation, Raritan, New Jersey, for serological testing. The report on the patient’s red blood cells suggested that "the only surviving cells were those of the baby, and that we might not be detecting any of [the patient’s] blood. This does not seem feasible." In 1968 a patient with acute granulocytic leukaemia was given cord blood and again we felt we had a take. We found changes in the Fy’ and S factors, suggesting a transplant. The patient received chemotherapy. We did not publish this case because some of the blood used for testing antigens had haemolysed. The patient survived for more than 8 months, which was very unusual in such cases. In 1972 we published an article in Virginia Medical Monthly.2 This was a case of acute lymphoblastic leukaemia which by the means then available (HLA typing was in its infancy in 1970 when the patient was treated) proved we had a transplant. This patient lived for nearly a year after the graft, which again was most unusual. use
we
Milton Ende 121 S Market Street,
2
WD1 1QH,
a case
blood and
Petersburg,
VA
23803, USA
Ende U. Lymphangiosarcoma: report of a case. Pacific Med Surg 1966; 74: 80-82. Ende M, Ende N. Hematopoietic transplantation by means of fetal (cord) blood: a new method. Virginia Med Mon 1972; 99: 276. Ende N. Use of human umbilical cord blood for stem cell transplantation (HLA matched, unmatched; clinical; ethical, and legal aspects). In: Hematopoietic stem cells: biology and therapeutic applications. New York: Marcel Dekker, 1995.
Quality of chloroquine preparations marketed in Dar es Salaam, Tanzania SiR-Although chloroquine treatment failures in malaria are usually due to drug resistance, low compliance or the use of chloroquine preparations of poor quality could also be the reason. During screening tests for chloroquine intake we encountered a patient with a negative Haskins test even though she claimed to have taken chloroquine 2 days earlier. Since the sales of drugs of poor quality have been reported in Africa and elsewhere,1-4 we immediately suspected that the tablets she had taken were not genuine. Unfortunately, the patient did not have any tablets left. However, the incident prompted a small survey. One of us (GR) visited several pharmacy shops in Dar es Salaam and collected samples of chloroquine tablets of nine different brands marketed in the city. The tablets were properly stored and then sent to Sweden for quality control at the central laboratory of the National Corporation of Swedish Pharmacies, Stockholm (US Pharmacopeia, edition XXII). Tablets were tested for active ingredients and for dissolution rate. All brands complied with the USP requirements for amount of chloroquine (>97%). The eight brands of ordinary tablets also passed the dissolution test; the sugar-coated tablets did not (only 39% dissolved in 45 min, required minimum 75%). Drug dissolution is an important determinant of bioavailability. We do not know if this was the chloroquine preparation our patient took. In a recent study in Sudan one chloroquine brand manufactured locally had less than half the area under the plasma concentration curve of the imported brands5 and the preparation that did not comply with the dissolution test in our study was one produced locally in Tanzania. It would be of interest to explore this problem in other African countries that have local production capacity. *Yakoub Aden Abdi, Gerald Rimoy, Örjan Ericsson, Christina Alm, Amos Y Massele *Division of Clinical Pharmacology, Department of Medical Sciences and Technology, Karolinska Institute and Hospital Pharmacy, Huddinge University Hospital, S-14186 Huddinge, Sweden; and Department of Clinical Pharmacology, Muhimbili Medical Center, Dar Es Salaam, Tanzania
1
2 3 4 5
Murtada M, Sesay B. Expiry dates on pharmaceuticals—some worrying realities in Sierra Leone. Int Pharm J 1994; 8: 202-06. Abu-Reid IO, El-Samani SA, Hag Omer AI, et al. Stability of drugs in the tropics: a study in Sudan. Int Pharm J 1990; 4: 6-10. Dennis P, Edghill LA, Allen M, Acheampong YB. Quality control of pharmaceuticals in the Caribbean. Int Pharm J 1992; 6: 64-68. Kibwage IO, Ogeto JO, Maitai CK, et al. Drug quality control work in Daru: observations during 1983-1986. E Afr Med J 1992; 69: 577-80. Mahmoud BM, Ali HM, Homeida MMA, Bennett JL. Bioequivalence of five chloroquine brands marketed in Sudan. Int Pharm J 1994; 8: 164-67.
1161