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factor in some cases of bacterial meningitis,3 and we suggest thatinvestigations of adult patients with high concentrations of IgG andunusual infections should include IgG subclass analysis.

Service de Medecine B,Labortoire de Biochemie,CHU de Nancy,Vandoeuvre le 54511,Nancy, France

CLAUDE JEANDELJEAN-LOUIS GUEANTNADINE PETIPAINMARIE-CHRISTINE LAURAINM. D. PIERRE JOUANNY

1. Harbug TD, Leonard HA, Kimbrouth RC, Jones SR. Group B streptococcalmeningitis appearing as acute deafness in a adult. Arch Neurol 1984; 41: 214-16.

2. Niklasson P, Back E, Kalin M, Wadstrom T. Group B streptococcal meningitis inchildren and adults. Scand J Infect Dis 1976; 8: 165-68.

3. Loh RK, Thong YH, Ferrante A Defidency of IgG subclasses and IgA, and elevationof IgE in children with a past history of bacterial meningitis. Acta Paediatr Scand1991; 80: 654-58.

Bone-marrow transplantation in sickle-cellanaemia: why so few so late?

SIR,-Although bone-marrow transplantation (BMT) isindicated for the treatment of genetic disorders of the bone marrow,it is rarely used in sickle-cell anaemia. There are only two reports ofsickle-cell anaemia treated with BMT in the USA and in both cases,BMT was for a different coexistent indication (acute myelogenousleukaemial and Morquio’s disease). 13 sickle-cell anaemia patientshave been reported to have received BMT, 1-5 and an additional 9 areunreported but mentioned by Kirkpatrick et al.6 Most of thesepatients received BMT in Belgium or France. The outcome ofBMT in these patients seems encouraging since only 1 (withcoexistent acute lymphocytic leukaemia) died and the remaining 21are alive with haemoglobin electrophoresis showing either AA(normal) or AS (sickle-cell trait). So why the delay in the

implementation of BMT for sickle-cell anaemia in the USA? Thepresumed low probability of cure, the fact that patients withsickle-cell anaemia are generally not threatened with immediatedeath, and the cost-effectiveness of the procedure created a

controversy for such use of BMT.We have collected data on the cost of health-care use by our adult

patients with sickle-cell anaemia. We used six indicators: (1)admissions, (2) attending physician and consultant fees for

inpatients, (3) clinic visits, (4) accident-and-emergency departmentvisits, (5) cost of diagnostic procedures (eg, laboratory, radiography,scans) and consultations for outpatients, and (6) cost of

prescriptions. In 1991, there were 654 admissions in 104 patients,1056 clinic visits in 125 patients, and 969 accident-and-emergencydepartment visits in 111 patients. 6759 days were spent in hospitalwith an average length of stay of 10 days. The total charge forhealth-care use was about$112 350 per patient per year (table).Assuming that an adult patient with sickle-cell anaemia will befollowed up for 15 years between the ages of 18 and 33 (the averageage of our adult patients), the total charge per patient would be$1685 250. This figure does not take into consideration the cost ofcare in childhood and the fact that most of our patients areunemployed and dependent on social security benefits. Also

hospitals, physicians, the accident-and-emergency department, andlaboratories receive only a small fraction of the charge listed in thetable in reimbursements, which discourages hospitals and

FINANCIAL ANALYSIS OF HEALTH-CARE USE BY PATIENTS WITHSICKLE-CELL ANAEMIA (1991)

*Attendmg physician of inpatients and consultants charge average of$50 per daytMinimum fee includes$250 for use of facjhty+$30 for complete blood count,platelet, and reticulocyte counts+$106 for attending physician’s fee.tAverage of 35 prescriptions are written per patient per year.

physicians from taking care of these patients on a routine andregular basis.The estimated charge for BMT, on the other hand, is about

$200 000. Thus a successful BMT in early childhood will generatesubstantial total savings and result in a healthy productiveindividual. If cost is a major factor in the risk/benefit ratio of BMTin sickle-cell anaemia, the ratio is obviously in favour of benefit.

Cardeza Foundation for Hemalological Research,Department of Medicine,Thomas Jefferson University Hospital,Philadelphia, Pennsylvania 19107, USA SAMIR K. BALLAS

1. Johnson LF, Look AT, Gockerman J, Ruggierro MR, Dalla Prozza G, Billings FT.Bone marrow transplantation in a patient with sickle cell anemia. N Engl J Med1984; 311: 780-83.

2. Mentzer WC, Packman S, Wara W, Morton C. Successful bone marrow transplant ina child with sickle cell anemia and Morquio’s disease. Blood 1990; 76: 69a.

3. Vermylen C, Fernandez Robles E, Ninane J, Cornu G. Bone marrow transplantationin five children with sickle cell anaemia. Lancet 1988; i: 1427-28.

4. Milpied N, Harousseau J, Garand R, David A. Bone marrow transplantation for sicklecell anaemia. Lancet 1988; ii: 328-29

5. Ferster A, DeValck C, Azzi N, Fondu P, Toppet M, Sariban E Bone marrowtransplantation for severe sickle cell anaemia. Br J Haematol 1992; 80: 102-05.

6. Kirkpatrick DV, Barrios NJ, Hambert JH. Bone marrow transplantation for sickle cellanemia. Semin Hematol 1991; 28: 240-43.

HIV infection and immune system in genesisof coronary lesions

SIR,-Dr Tabib and colleagues (Sept 19, p 730) report strikingcoronary lesions after unexplained deaths in young HIV-positivesubjects without risk factors for atherosclerosis. They suggest thatvirus-induced endothelial injury is the cause of this acceleratedatherosclerosis. However, although they provide no data about thepresence of old or fresh infarct and histopathological features thatare often associated with sudden death (fissured plaque, attachedthrombosis, and peripheral emboli of platelet aggregates), theiranecdotal fmdings bring additional support to the view that theimmune system is implicated in accelerated atherosclerosis.’ Organtransplant recipients also develop accelerated atherosclerosis,sometimes called chronic rejection. Indeed, chronic immunevascular damage and cytomegalovirus infection or reinfection havebeen proposed as possible contributors to graft atherosclerosis.However, in both transplanted patients and HIV-infected subjects,the genesis of coronary lesions can be viewed quite differently.

HIV-infected individuals and cyclosporin-treated transplantedpatients have in common a major inhibition of CD4 T lymphocyteswhich prevents them from responding to foreign antigens; themonocyte-macrophage system, however, is stimulated in responseto HIV-infection, foreign antigen, or opportunistic infection, whichinduces a striking change in the cytokine cascade regulation andmay result in uncontrolled fibrous intimal growth. In fact, there aremany activated CD4 T-lymphocytes in the human, slow-growing,spontaneous atherosclerotic plaque.! Experimental studies haveshown that interferon-y, a secretory product of activatedT lymphocytes, acts as a natural regulator of smooth muscle cellmultiplication in culture2 and is a potent inhibitor of the formationof intimal proliferative lesion in vivo.3 Thus, the presence of CD4cells in coronary lesions may be protective. Virus-induced orcyclosporin-induced T-lymphocyte inhibition may result in a localdeficiency in interferon-y and intimal fibrosis, as well as lipidinfiltration, since interferon-y treatment reduces intracellular

cholesteryl ester accumulation and inhibits the development ofmacrophage-derived foam cells.’ In addition, interferon seems tolower systemic low-density-lipoprotein (LDL) cholesterol andapolipoprotein B concentrations.5By contrast, interleukin-1 and tumour necrosis factor, produced

by monocyte-macrophage and stimulated vascular smooth musclecells, may participate in autocrine and paracrine growth stimulationof fibrous intimal proliferation.6 The development of acceleratedatherosclerosis in arteries of HIV-infected subjects and graftrecipients may thus represent an arterial manifestation ofimmunosuppression, whatever the cause, mediated largely by aregionally acting (or not acting) cytokine network. Furthermore, inboth HIV-infected patients7 and heart transplant recipients,8