- Email: [email protected]
PLASMA LEAD AND CISPLATTN
624 for All, aimed at strengthening primary health care and multi-sector cooperation, and integrating AIDS into strengthened health care and educational systems, so-called vertical programmes that are heavily centralised are being established. There seems to be a tendency to make health and AIDS the context for renewed cultural imperialism. Are ex-patriate health consultants the new colonialists? Health for All gives the framework for a valid approach to control of the spread of HIV, and provision of services for people with AIDS, and requires international cooperation. But the recognition of economic stresses, limited resources, the threat to whole families, and unmeasured attrition rate due to HIV in Africa make it imperative that the conference circuit of the professionals decreases while down-to-earth prevention interventions through community-based programmes increase. 35 Westgarth Gardens, Bury St Edmunds, Suffolk IP33 3LG
J. D. HARVEY
CLASSICAL COMPLEMENT PATHWAY IN HIV INFECTION
SIR,-17he CD4 molecule is not the only port of entry by which HIV may infect target cells.1,2 Dr Soelder and colleagues (July 29, p 271) provide evidence that, after opsonisation by complement, HIV acquires the ability to infect cultured monoblastoid cells via complement receptor 3 (CR3). They conclude that components of the classical complement pathway3 and CR3 may combine to provide a mode of entry for the virus into CR3-expressing cells, such as those of monocyte/macrophage lineage, which are important reservoirs for HIV.4 If this in-vitro mechanism has a role in the pathogenesis of HIV infection in vivo, one would expect to find activation of the classical pathway in those infected with HIV: we can provide such evidence. We measured C4d and C3d, fragments of C4 and C3 cleaved after classical pathway activation, by nephelometry5,6in EDTA-plasma from 74 people with HIV infection (69 male, mean aged 34 years, range 22-45). 33 were symptom-free (CDC stage II), 9 were stage III (persistent generalised lymphadenopathy), 9 were IVA (AIDSrelated complex), and 23 had AIDS (stage IVB, C, D). We also studied 32 healthy controls (26 male, mean age 33 years, range 27-47). Results were expressed as percentages of a 100% standard preparation, and evaluated by Student’s t test and analysis of variance with tests for linearity. Values of C4d and C3d were significantly higher in those with HIV infection than in controls (table). Moreover, the more advanced the CDC stage the bigger the difference. Activation of the classical pathway occurs at every stage in HIV infection and reflects disease severity. This is consistent with the virus itself contributing to such activation, since HIV replication and dissemination increase in the later stages of infection.7 Opsonisation would enable the virus to bind and gain entry into MEAN (SD) AND THEIR STATISTICAL COMPARISON IN SUBJECTS WITH HIV INFECTION AND CONTROLS
CR3-expressing cells. Our data therefore accord with the conclusion of Soelder et al that a mechanism of cell entry involving the classical complement pathway may be of pathogenic relevance in HIV infection. G. SENALDI M. PEAKMAN T. MCMANUS Departments of Immunology and Genito-urinary Medicine, E. T. DAVIES King’s College School D. E. H. TEE of Medicine and Dentistry, D. VERGANI London SE5 8RX 1. Robinson WE Jr, Montefiori DC, Mitchell WM. Antibody-dependent enhancement of human immunodefiency virus type 1 infection. Lancet 1988; i: 790-94.
CU, Ennis FA. Antibody-enhanced infection by HIV-1 via Fc Science 1988; 242: 580-83. 3. Soelder BM, Schultz TF, Hengster P, et al. HIV and HIV infected cells differentially activate the complement system. Immunol Lett 1989; 22: 135-46. 4. Ho DD, Rota TR, Hirsh MS. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest 1986; 77: 1712-19. 5. Davies ET, Nasaruddin BA, Alhaq A, Senaldi G, Vergani D. Clinical application of a new technique measuring C4d for the assessment of activation of the classical complement pathway. J Clin Pathol 1989; 41: 143-47. 6. Vergani D, Bevis L, Nasaruddin BA, Mieli-Vergani G, Tee DEH. Clinical application of a new laser nephelometric technique to measure complement activation. J Clin Pathol 1983; 36: 793-99. 7. Allain JP, Laurian Y, Paul DA, et al. Long-term evaluation of HIV antigen and antibodies to p24 and gp41 in patients with hemophilia: potential clinical importance. N Engl J Med 1987; 317: 1114-21. 2. Takeda A, Tuazon
receptor-mediated entry.
PLASMA LEAD AND CISPLATTN
SIR,-Dr Tothill and colleagues (Aug 5, p 333) report plasma lead concentrations in patients before and after treatment with cisplatin. They conclude that their results are inconsistent with the cisplatin-induced transfer of lead to kidney tissue which we
reported.1 Pre-treatment plasma lead concentrations in their patients ranged from 20 to 160 ng/ml (mean about 60). This is about half the expected whole blood lead concentration in people not abnormally exposed to lead. Less than 1% of whole blood lead is present in plasma.2-4 Tothill and colleagues concede that some of their samples are contaminated with lead but in our view the contamination is too great for any conclusions to be drawn from their data. Heparin is a possible source of the contamination.5 After cisplatin, plasma lead concentrations of over 200 ng/ml were observed. Assuming a renal plasma flow of 600 ml/min, over 170 mg of lead would be available for renal uptake in 24 h. This would be adequate to explain the effect which we observed. We cannot therefore understand why it has been concluded that cisplatin does not mobilise lead. We agree that the immediate source of the lead which is taken up by the kidney after cisplatin is likely to be the plasma lead pool because it turns over much more rapidly than the erythocyte pool. We are now measuring plasma lead during cisplatin treatment. Departments of Chemical Pathology and Medical Physics, Singleton Hospital, Swansea SA2 8QA
IAN R. HAINSWORTH W. D. MORGAN
AM, Morgam WD, Cobbold S, et al. Unexpected mobilisation of lead during cisplatin chemotherapy. Lancet 1986; ii: 249-50. 2. Everson J, Patterson CC. "Ultra-clean" isotope dilution/mass spectrometric analysis for lead in human blood plasma indicate that most reported values are artificially high. Clin Chem 1980; 26: 1603-07. 3. Desilva PE. Determination of lead in plasma and studies on its relationship to lead in erythrocytes. Br J Ind Med 1981; 38: 209-17. 4. Manton WI, Cook JD. High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid. Br J Ind Med 1984; 41: 313-19. 5. Ong CN, Phoon WO, Lee BL, et al. Lead in plasma and its relation to other biological indicators. Ann Occup Hyg 1986; 30: 219-28. 1. El-Sharkawi
INTESTINAL "LUCID INTERVAL" AND PHYTOBEZOAR ILEUS Values for C4d and C3d relate to log transformations, used to lessen problem of unequal variances. and tp<001 *p<0001 accompanying mean (SD) refer to differences between HIV-infected groups and controls. F 4,10 summarises the overall analysis, and the larger its value the greater the evidence against the null hypothesis that the group means are equivalent. ; j 01 and F 3,10should be considered together in assessing the trend (linear or non-linear) across groups. Low values suggest no trend; a high f)jo) and low F3,10, indicate a linear trend.
SiR,-Bezoars in the gastrointestinal cause small-bowel obstruction/,2
tract
after
gastric surgery
and in Israel the high incidence of persimmon bezoar is a cause of concern. Krausz et al4 have defined some clinical aspects of bezoar ileus that might differentiate it from other causes of intestinal obstruction. However, the differential diagnosis between small-bowel obstruction due to can
J. D. HARVEY
CLASSICAL COMPLEMENT PATHWAY IN HIV INFECTION
SIR,-17he CD4 molecule is not the only port of entry by which HIV may infect target cells.1,2 Dr Soelder and colleagues (July 29, p 271) provide evidence that, after opsonisation by complement, HIV acquires the ability to infect cultured monoblastoid cells via complement receptor 3 (CR3). They conclude that components of the classical complement pathway3 and CR3 may combine to provide a mode of entry for the virus into CR3-expressing cells, such as those of monocyte/macrophage lineage, which are important reservoirs for HIV.4 If this in-vitro mechanism has a role in the pathogenesis of HIV infection in vivo, one would expect to find activation of the classical pathway in those infected with HIV: we can provide such evidence. We measured C4d and C3d, fragments of C4 and C3 cleaved after classical pathway activation, by nephelometry5,6in EDTA-plasma from 74 people with HIV infection (69 male, mean aged 34 years, range 22-45). 33 were symptom-free (CDC stage II), 9 were stage III (persistent generalised lymphadenopathy), 9 were IVA (AIDSrelated complex), and 23 had AIDS (stage IVB, C, D). We also studied 32 healthy controls (26 male, mean age 33 years, range 27-47). Results were expressed as percentages of a 100% standard preparation, and evaluated by Student’s t test and analysis of variance with tests for linearity. Values of C4d and C3d were significantly higher in those with HIV infection than in controls (table). Moreover, the more advanced the CDC stage the bigger the difference. Activation of the classical pathway occurs at every stage in HIV infection and reflects disease severity. This is consistent with the virus itself contributing to such activation, since HIV replication and dissemination increase in the later stages of infection.7 Opsonisation would enable the virus to bind and gain entry into MEAN (SD) AND THEIR STATISTICAL COMPARISON IN SUBJECTS WITH HIV INFECTION AND CONTROLS
CR3-expressing cells. Our data therefore accord with the conclusion of Soelder et al that a mechanism of cell entry involving the classical complement pathway may be of pathogenic relevance in HIV infection. G. SENALDI M. PEAKMAN T. MCMANUS Departments of Immunology and Genito-urinary Medicine, E. T. DAVIES King’s College School D. E. H. TEE of Medicine and Dentistry, D. VERGANI London SE5 8RX 1. Robinson WE Jr, Montefiori DC, Mitchell WM. Antibody-dependent enhancement of human immunodefiency virus type 1 infection. Lancet 1988; i: 790-94.
CU, Ennis FA. Antibody-enhanced infection by HIV-1 via Fc Science 1988; 242: 580-83. 3. Soelder BM, Schultz TF, Hengster P, et al. HIV and HIV infected cells differentially activate the complement system. Immunol Lett 1989; 22: 135-46. 4. Ho DD, Rota TR, Hirsh MS. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest 1986; 77: 1712-19. 5. Davies ET, Nasaruddin BA, Alhaq A, Senaldi G, Vergani D. Clinical application of a new technique measuring C4d for the assessment of activation of the classical complement pathway. J Clin Pathol 1989; 41: 143-47. 6. Vergani D, Bevis L, Nasaruddin BA, Mieli-Vergani G, Tee DEH. Clinical application of a new laser nephelometric technique to measure complement activation. J Clin Pathol 1983; 36: 793-99. 7. Allain JP, Laurian Y, Paul DA, et al. Long-term evaluation of HIV antigen and antibodies to p24 and gp41 in patients with hemophilia: potential clinical importance. N Engl J Med 1987; 317: 1114-21. 2. Takeda A, Tuazon
receptor-mediated entry.
PLASMA LEAD AND CISPLATTN
SIR,-Dr Tothill and colleagues (Aug 5, p 333) report plasma lead concentrations in patients before and after treatment with cisplatin. They conclude that their results are inconsistent with the cisplatin-induced transfer of lead to kidney tissue which we
reported.1 Pre-treatment plasma lead concentrations in their patients ranged from 20 to 160 ng/ml (mean about 60). This is about half the expected whole blood lead concentration in people not abnormally exposed to lead. Less than 1% of whole blood lead is present in plasma.2-4 Tothill and colleagues concede that some of their samples are contaminated with lead but in our view the contamination is too great for any conclusions to be drawn from their data. Heparin is a possible source of the contamination.5 After cisplatin, plasma lead concentrations of over 200 ng/ml were observed. Assuming a renal plasma flow of 600 ml/min, over 170 mg of lead would be available for renal uptake in 24 h. This would be adequate to explain the effect which we observed. We cannot therefore understand why it has been concluded that cisplatin does not mobilise lead. We agree that the immediate source of the lead which is taken up by the kidney after cisplatin is likely to be the plasma lead pool because it turns over much more rapidly than the erythocyte pool. We are now measuring plasma lead during cisplatin treatment. Departments of Chemical Pathology and Medical Physics, Singleton Hospital, Swansea SA2 8QA
IAN R. HAINSWORTH W. D. MORGAN
AM, Morgam WD, Cobbold S, et al. Unexpected mobilisation of lead during cisplatin chemotherapy. Lancet 1986; ii: 249-50. 2. Everson J, Patterson CC. "Ultra-clean" isotope dilution/mass spectrometric analysis for lead in human blood plasma indicate that most reported values are artificially high. Clin Chem 1980; 26: 1603-07. 3. Desilva PE. Determination of lead in plasma and studies on its relationship to lead in erythrocytes. Br J Ind Med 1981; 38: 209-17. 4. Manton WI, Cook JD. High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid. Br J Ind Med 1984; 41: 313-19. 5. Ong CN, Phoon WO, Lee BL, et al. Lead in plasma and its relation to other biological indicators. Ann Occup Hyg 1986; 30: 219-28. 1. El-Sharkawi
INTESTINAL "LUCID INTERVAL" AND PHYTOBEZOAR ILEUS Values for C4d and C3d relate to log transformations, used to lessen problem of unequal variances. and tp<001 *p<0001 accompanying mean (SD) refer to differences between HIV-infected groups and controls. F 4,10 summarises the overall analysis, and the larger its value the greater the evidence against the null hypothesis that the group means are equivalent. ; j 01 and F 3,10should be considered together in assessing the trend (linear or non-linear) across groups. Low values suggest no trend; a high f)jo) and low F3,10, indicate a linear trend.
SiR,-Bezoars in the gastrointestinal cause small-bowel obstruction/,2
tract
after
gastric surgery
and in Israel the high incidence of persimmon bezoar is a cause of concern. Krausz et al4 have defined some clinical aspects of bezoar ileus that might differentiate it from other causes of intestinal obstruction. However, the differential diagnosis between small-bowel obstruction due to can