551
ICU OUTCOMEAND MEAN DA!LYT!SSATGUY’SHOSP!TAL, 1991
In our unit, only when TISS is more than 40 points do we see such a mortality rate (table). Moreover, in the past six months, the mean daily TISS for patients with APACHE II scores of 15-25 at Guy’s was 38 points. The discrepancy between mortality and TISS in the Argentinian study casts doubt on whether their small changes in therapy, guided by pHi measurement, were likely to have had any discernible effect on outcome. Another point concerns the substantial proportion of patients, 44% in this study and 38% in their previous study,l in whom pHi deteriorated over the first 24 h despite therapy. This is in striking contrast to our own findings in which only 8 % of patients showed this pattem.2 Even more disconcertingly, no improvement in survival could be demonstrated in the group with a low pHi on admission, despite the fact that in Gutierrez and co-workers’ previous report1 patients in whom a low pHi became normal over 12 h had a pronounced reduction in mortality rate (65-4% to 36-4%). We have been able to confirm this observation, and the lack of effect of their treatment protocol in this high-risk group casts doubt on its ability to alter pHi. We believe that this study demonstrates little more than the
prognostic importance of pHi
in critically ill patients and fails to resolve the issue of whether its manipulation improves outcome.
Departments of Surgery and Guy’s Hospital,
Intensive Care,
London SE1 9RT, UK
NICHOLAS MAYNARD RICHARD BEALE MARK SMITHIES DAVID BIHARI
favour of an experimental HIV vaccine.3 Another showed that four patients with pneumonia developed severe bone-marrow aplasia 12 weeks after initiation of AZT; three recovered within 4 weeks of discontinuation of the drug.4 Moreover, there is no proof that HIV causes AIDS.l It follows that AZT therapy for antibody-positive persons is indeed a "cause for concern". In view of this I can understand why Wellcome, the producer of AZT, declined an invitation to discuss these concerns with Meditel, the programme’s producers, but it seems arrogant for medical scientists running the Anglo-French Concorde trial of AZT to decline as well. Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
Duesberg PH. AIDS epidemiology: inconsistencies with human immunodeficiency virus and with infectious disease. Proc Natl Acad Sci USA 1991; 88: 1575-79. 2. Duesberg PH. The role of drugs in the origin of AIDS. Biomed Phamacother 1992; 46: 1.
3-15. 3. Scolaro M, Durham R, Pieczenik G. Potential molecular competitor for HIV. Lancet 1991; 337: 731-32. 4. Gill PS, Rarick M, Byrnes RK, Causey D, Loureiro C, Levme AM. Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107: 502-05.
HIV
Paid donations
HlVpositive No Rate (per 105) Risk ratio (and 95%
(in press).
HIV
as
Scoring System: update 1983. Crit
target for zidovudine
SIR,-Your note (Feb 15, p 421) on a British television documentary on zidovudine (azidothymidine, AZT) asserts that HIV undergoes antigenic drift and "is constantly able to escape" neutralising antibodies and is thus a legitimate target for AZT
therapy. A legitimate target is one that is susceptible to DNA chain termination by AZT because it is actively engaged in DNA synthesis. However, there is no evidence that HIV drifts antigenically in antibody-positive persons, in the presence or absence of AZT. For example, the "AID S test" only works because antibodies against HIV from all virus carriers react with the same patented, standard HIV strain. Indeed, only a minority of viral antigens can drift without eliminating the viability of a virus, which is the reason that vaccines work. If viruses in general could evade immunity by antigenic drift, the immune system would be little more than a vestigial burden to the host. The television programme pointed out, correctly, that HIV is not a legitimate target for inhibition with a chain terminator of DNA synthesis in people with antibodies against HIV. No study has detected HIV DNA synthesis from viral DNA, and virtually none has found free HIV in such people, because antiviral immunity effectively inhibits HIV replication to undetectable levels.l This is why it is notoriously difficult to isolate HIV from AID S patients. In antibody-positive individuals AZT can only inhibit that HIV proviral DNA which is already integrated into cell DNA; in other words it has to kill the cell to inhibit HIV. Since only 1 in 500 T-cells contains HIV DNA, AZT must kill 500 uninfected cells to kill just HIV-infected cell.2 Several studies demonstrate the resulting toxicity of AZTOne of these, published in The Lancet, demonstrated that 10 of 11 AIDS patients recovered cellular immunity on discontinuing AZT in one
seropositivity in paid blood donors
SiR,—European Community directive 89/381 demands "the production and use of products derived from human blood or human plasma coming from voluntary unpaid donations". Whether the implementation of this requirement will improve the safety of blood supplies in Europe is still being debated. Since in other European countries information about the impact of paying donors on blood product safety is scarce, data from Germany may be of interest. Over 6 million randomly selected blood and plasma donations, collected in different regions of former West Germany between 1985 and 1991, show the following picture:
1. Doglio G, Pusajo J, Egurrola M, et al. Gastric mucosal pH as a prognostic index of mortality in critically ill patients. Crit Care Med 1991; 19: 1037-40. 2. Maynard ND, Bihari D, Mason R, et al. A comparison between gastric intramucosal pH and pulmonary artery oxygen transport measurements on the ITU. Br J Surg 3. Keene AR, Cullen DJ. Therapeutic Intervention Care Med 1983; 11: 1-3.
PETER H. DUESBERG
CI)
(n=1447 290J
Unpaid donations (n 4670 257)
222 15-34
90 1-93 8-0
=
(6-2-10-2)
These figures suggest that with remunerated donations measures aimed at eliminating at-risk donors before laboratory screening are not
effective enough.
Red Cross Blood Donation Service, 4400 Munster, Germany
H. FIEDLER
Exposure to chemicals and development of malignant disease SiR,-Your Feb 1 editorial about a possible association of brain gliomas and industrial or hospital laboratory chemical exposure has important implications for further epidemiological research and industrial practice. We report two cases of malignant gliomas in fairly young patients who had prolonged exposure to volatile reactive organic compounds in the chemical industry. Both patients were non-smokers and no other potential cause of malignant disease could be identified. Patient 1-A 41-year-old man presented with paraesthesiae of the right fingertips followed by a progressive right hemiparesis. Computed tomography (CT) revealed a left frontoparietal tumour, which was histologically grade III-IV astrocytoma. The patient had worked for 25 years in the chemical industry and had been exposed to chemicals used in the production of vinylidene chloride and other solvents. Patient 2-A 43-year-old man presented with frontal headaches, nausea, tremor, and difficulty with fine movements of the right hand. CT revealed a large left frontoparietal tumour, which proved to be a glioblastoma multiforme on histology. The patient had been closely involved in the development of paraquat production with exposure to agents such as 4,4’ bipyridyl. We are also concerned about the pattern of registration for brain tumours reported by the Mersey Cancer Registry (1983-87). The standardised registration ratios (SRRs) for all health districts in the Mersey region were calculated with the England and Wales cancer
ICU OUTCOMEAND MEAN DA!LYT!SSATGUY’SHOSP!TAL, 1991
In our unit, only when TISS is more than 40 points do we see such a mortality rate (table). Moreover, in the past six months, the mean daily TISS for patients with APACHE II scores of 15-25 at Guy’s was 38 points. The discrepancy between mortality and TISS in the Argentinian study casts doubt on whether their small changes in therapy, guided by pHi measurement, were likely to have had any discernible effect on outcome. Another point concerns the substantial proportion of patients, 44% in this study and 38% in their previous study,l in whom pHi deteriorated over the first 24 h despite therapy. This is in striking contrast to our own findings in which only 8 % of patients showed this pattem.2 Even more disconcertingly, no improvement in survival could be demonstrated in the group with a low pHi on admission, despite the fact that in Gutierrez and co-workers’ previous report1 patients in whom a low pHi became normal over 12 h had a pronounced reduction in mortality rate (65-4% to 36-4%). We have been able to confirm this observation, and the lack of effect of their treatment protocol in this high-risk group casts doubt on its ability to alter pHi. We believe that this study demonstrates little more than the
prognostic importance of pHi
in critically ill patients and fails to resolve the issue of whether its manipulation improves outcome.
Departments of Surgery and Guy’s Hospital,
Intensive Care,
London SE1 9RT, UK
NICHOLAS MAYNARD RICHARD BEALE MARK SMITHIES DAVID BIHARI
favour of an experimental HIV vaccine.3 Another showed that four patients with pneumonia developed severe bone-marrow aplasia 12 weeks after initiation of AZT; three recovered within 4 weeks of discontinuation of the drug.4 Moreover, there is no proof that HIV causes AIDS.l It follows that AZT therapy for antibody-positive persons is indeed a "cause for concern". In view of this I can understand why Wellcome, the producer of AZT, declined an invitation to discuss these concerns with Meditel, the programme’s producers, but it seems arrogant for medical scientists running the Anglo-French Concorde trial of AZT to decline as well. Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
Duesberg PH. AIDS epidemiology: inconsistencies with human immunodeficiency virus and with infectious disease. Proc Natl Acad Sci USA 1991; 88: 1575-79. 2. Duesberg PH. The role of drugs in the origin of AIDS. Biomed Phamacother 1992; 46: 1.
3-15. 3. Scolaro M, Durham R, Pieczenik G. Potential molecular competitor for HIV. Lancet 1991; 337: 731-32. 4. Gill PS, Rarick M, Byrnes RK, Causey D, Loureiro C, Levme AM. Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1987; 107: 502-05.
HIV
Paid donations
HlVpositive No Rate (per 105) Risk ratio (and 95%
(in press).
HIV
as
Scoring System: update 1983. Crit
target for zidovudine
SIR,-Your note (Feb 15, p 421) on a British television documentary on zidovudine (azidothymidine, AZT) asserts that HIV undergoes antigenic drift and "is constantly able to escape" neutralising antibodies and is thus a legitimate target for AZT
therapy. A legitimate target is one that is susceptible to DNA chain termination by AZT because it is actively engaged in DNA synthesis. However, there is no evidence that HIV drifts antigenically in antibody-positive persons, in the presence or absence of AZT. For example, the "AID S test" only works because antibodies against HIV from all virus carriers react with the same patented, standard HIV strain. Indeed, only a minority of viral antigens can drift without eliminating the viability of a virus, which is the reason that vaccines work. If viruses in general could evade immunity by antigenic drift, the immune system would be little more than a vestigial burden to the host. The television programme pointed out, correctly, that HIV is not a legitimate target for inhibition with a chain terminator of DNA synthesis in people with antibodies against HIV. No study has detected HIV DNA synthesis from viral DNA, and virtually none has found free HIV in such people, because antiviral immunity effectively inhibits HIV replication to undetectable levels.l This is why it is notoriously difficult to isolate HIV from AID S patients. In antibody-positive individuals AZT can only inhibit that HIV proviral DNA which is already integrated into cell DNA; in other words it has to kill the cell to inhibit HIV. Since only 1 in 500 T-cells contains HIV DNA, AZT must kill 500 uninfected cells to kill just HIV-infected cell.2 Several studies demonstrate the resulting toxicity of AZTOne of these, published in The Lancet, demonstrated that 10 of 11 AIDS patients recovered cellular immunity on discontinuing AZT in one
seropositivity in paid blood donors
SiR,—European Community directive 89/381 demands "the production and use of products derived from human blood or human plasma coming from voluntary unpaid donations". Whether the implementation of this requirement will improve the safety of blood supplies in Europe is still being debated. Since in other European countries information about the impact of paying donors on blood product safety is scarce, data from Germany may be of interest. Over 6 million randomly selected blood and plasma donations, collected in different regions of former West Germany between 1985 and 1991, show the following picture:
1. Doglio G, Pusajo J, Egurrola M, et al. Gastric mucosal pH as a prognostic index of mortality in critically ill patients. Crit Care Med 1991; 19: 1037-40. 2. Maynard ND, Bihari D, Mason R, et al. A comparison between gastric intramucosal pH and pulmonary artery oxygen transport measurements on the ITU. Br J Surg 3. Keene AR, Cullen DJ. Therapeutic Intervention Care Med 1983; 11: 1-3.
PETER H. DUESBERG
CI)
(n=1447 290J
Unpaid donations (n 4670 257)
222 15-34
90 1-93 8-0
=
(6-2-10-2)
These figures suggest that with remunerated donations measures aimed at eliminating at-risk donors before laboratory screening are not
effective enough.
Red Cross Blood Donation Service, 4400 Munster, Germany
H. FIEDLER
Exposure to chemicals and development of malignant disease SiR,-Your Feb 1 editorial about a possible association of brain gliomas and industrial or hospital laboratory chemical exposure has important implications for further epidemiological research and industrial practice. We report two cases of malignant gliomas in fairly young patients who had prolonged exposure to volatile reactive organic compounds in the chemical industry. Both patients were non-smokers and no other potential cause of malignant disease could be identified. Patient 1-A 41-year-old man presented with paraesthesiae of the right fingertips followed by a progressive right hemiparesis. Computed tomography (CT) revealed a left frontoparietal tumour, which was histologically grade III-IV astrocytoma. The patient had worked for 25 years in the chemical industry and had been exposed to chemicals used in the production of vinylidene chloride and other solvents. Patient 2-A 43-year-old man presented with frontal headaches, nausea, tremor, and difficulty with fine movements of the right hand. CT revealed a large left frontoparietal tumour, which proved to be a glioblastoma multiforme on histology. The patient had been closely involved in the development of paraquat production with exposure to agents such as 4,4’ bipyridyl. We are also concerned about the pattern of registration for brain tumours reported by the Mersey Cancer Registry (1983-87). The standardised registration ratios (SRRs) for all health districts in the Mersey region were calculated with the England and Wales cancer
