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The statement that only 3 patients had cognitive impairment isperplexing. It would be expected that all patients with HIVencephalitis have ADC.3 Possible explanations for this discrepancyare that there was a non-neurologist assessment of ADC or thatpatient evaluation was remote from the time of death.

Discussion of possible mechanisms of neuronal loss shouldinclude quinolinic acid-a neurotoxin, acting via the N-methyl-D-aspartate receptor, which is increased in HIV-infected patients,especially those with ADC.4

National Centre in HIV Epidemiologyand Clinical Research,

St Vincent’s Medical Centre,Sydney, NSW 2010, Australia BRUCE JAMES BREW

1. Brew BJ, Sidtis J, Petito CK, Price RW. The neurological complications of AIDS andhuman immunodeficiency virus infection. In: Plum F, ed. Advances in

contemporary neurology. Philadelphia: FA Davis, 1988: 1-49.2. Tross S, Price RW, Navia B, et al. Neuropsychological characterization of the AIDS

dementia complex: a preliminary report. AIDS 1988; 2: 81-88.3. Price RW, Brew BJ, Sidtis J, Rosenblum M, Scheck AC, Cleary P. The brain in

AIDS: central nervous system HIV-1 infection and the AIDS dementia complex.Science 1988; 239: 586-92.

4. Heyes MP, Brew BJ, Martin A, et al. Qumolinic acid in the cerebrospinal fluid andserum in HIV-1 infection: relationship to clinical and neurological status. AnnNeurol 1991; 29: 202-09.

*** These letters have been shown to Dr Everall and colleagues,whose reply follows.-ED. L.

SIR,-Dr Reimund and Dr Martin mention the potentialcomplications of zidovudine. Clinical neurotoxicity, in the form ofseizures, has been attributed to this drugl but the neuropathologicaleffect of zidovudine is not known. Nor do we know the significanceof zidovudine globules in the brain. Nutritional and metabolicdisorders are important factors to be considered, but their

significance has not been established in AIDS. We are wellacquainted with the work referred to on pellagra2-it was done inthis department-but none of the characteristic features of pellagrawere found in our cases.While such confounding variables cannot be discounted, the

HIV-infected individuals we studied were collected over a five-yearperiod when treatment (including use ofzidovudine), physical state,and illness duration would have varied greatly since the

management of AIDS improved over this time. Nevertheless theneuronal numerical density of the HIV group was consistentlylower than that of the control group and the standard deviation wasmodest. This implies that the one consistent factor, HIV infection,was the principal reason for the neuronal loss.

All the salient histological features of our cases are in our paper.Many studies, of a variety of neurodegenerative disorders, identifyneuronal loss but not neurons "dropping-out". To support theirstatement that neuronal loss is often characterised by residualeosinophilic bodies Reimund and Martin cite a report of a patientwith a 41-year history of an unusual twilight state. 3There is now a lot of published work on toxic interactions

between the HIV envelope protein gp120 and neuronal receptors4as a cause of neuronal loss that is ascribed to HIV. In response to

your correspondents’ last question-yes, we are doing an extensivequantitative morphometric study of different areas of the brain,together with immunocytochemistry.Dr Emerich and Professor Sanberg raise issues about the

mechanism of the neuronal loss. Our study was to clarify, byquantitative morphometry, the association of HIV with neuronalloss. We discussed the role of gp120 in mediating this damage.Quinolinic acid an excitotoxin, binds to the NMDA receptor (asubtype of glutamate receptor), and seems to be an important factorin mediating gp 120 neurotoxicity. This neurotoxicity only occurs inthe presence of glutamate and the increased quinolinic acid is seen asan endogenous glutamate agonist that facilitates gp120 toxicity invivo.4 This interaction between gp120 and glutamate may alsoexplain the ability of NMDA antagonists to prevent mononuclearcells killing rat and chick neurons in vitros since analysis of thesoluble factors secreted by HIV-infected macrophages did notimplicate excitotoxins.6 Furthermore, HIV encephalitis isassociated with higher levels of unintegrated HIV DNA. However,

it is still not clear whether areas of inflammatory change in the brainare also those areas with striking neuronal loss.Dr Brew demonstrates the difficulty in correlating pathological

and clinical features. Subcortical dementia is a confusing term.Clinically, the syndrome has characteristic features; nonetheless,several of the diseases, it transpires, have histopathological lesions inthe cerebral cortex.B We concentrated on the neuropathologicalfeatures of HIV-associated brain disease and not on clinicalcorrelations. However, finding serious cortical neuronal loss doesnot per se support a subcortical dementia. Whilst Brew is correct toremark on the apparent correlation between HIV encephalitis andAIDS dementia complex the precise neuropathological substrateremains unclear.9 The demonstration of neuronal loss in cases withminimal pathological change suggests that neuronal loss and not thedegree of HIV encephalitis may present a pathological counterpartof ADC. The correlation of neuropathological and clinical featuresis a pressing issue and we agree entirely with Brew’s suggestion forfuture study.

Department of Neuropathology,Institute of Psychiatry,London SE5 8AF, UK

IAN EVERALLPHILIP LUTHERTPETER LANTOS

1. Hagler DN, Frame PT. Azidothymidine neurotoxicity. Lancet 1986; ii: 1392-93.2. Leigh D. Pellagra and the nutritional neuropathies: a neuropathological review, J Ment

Sci 1952; 98: 130-42.3. Arai N, Honda Y, Amano N, Yagishita S, Misugi K. Foamy spheroid bodies in the

substantia nigra. Report of an unusual case with recurrent attacks of peculiartwilight state. J Neurol 1988; 235: 330-34.

4. Lipton SA. HIV-related neurotoxicity. Brain Pathol 1991; 1: 193-99.5. Giullian D, Vaca K, Noonan CC. Secretion of neurotoxins by mononuclear

phagocytes infected with HIV-1. Science 1990; 250: 1593-966. Pulliam L, Herndier BG, Tang NM, McGrath MS. Human immunodeficiency

virus-infected macrophages produce soluble factors that cause histological andneurochemical alterations in cultured human brains. J Clin Invest 1991; 87: 503-12.

7. Pang S, Koyanagi Y, Miles S, Wiley C, Vinters HV, Chen ISY. High levels ofunintegrated HIV-1 DNA in brain tissue of AID S dementia patients. Nature 1990;343: 85-89.

8. Cummings JL, Benson DF. Subcortical dementia: review of an emerging concept.Arch Neurol 1984; 41: 874-79.

9. Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P. The brain in AIDS:central nervous system HIV-1 infection and AIDS dementia complex. Science1988; 239: 586-92.

Blood-pressure measurement in pregnancySiR,—Your May 18 editorial outlines three ways forward for

blood pressure measurement in pregnancy; automated

sphygmomanometers, self-monitoring, and use of systolic bloodpressure to defme hypertension. Although not widely studied, thereseems to be a substantial difference between the auscultated fourthand fifth sounds in patients with moderate or severe hypertension inpregnancy, and this difference increases with systolic blood

pressure-eg, a systolic blood pressure value of 170 mm Hg isassociated with an auscultated fourth sound recorded at 125 mm Hgand an auscultated fifth sound at 95 mm Hg.The widespread introduction of automated blood-pressure

measurement devices in delivery units means this difference is ofpractical importance, and may not be widely appreciated. Mostautomated devices display a diastolic blood pressure that

approximates to the auscultated fifth sound, yet the threshold forthe treatment of severe hypertension in many units is an auscultatedfourth sound at 110 mm Hg. With the use of automated devices thegoalposts have been changed, and if midwives and clinicians acceptuncritically the diastolic measurement from an automated device,the patient may be exposed to prolonged periods of sustained severehypertension with its attendant morbidity and mortality. Theseunfortunate consequences have been noted in three major teachingunits in the UK in the past twelve months.The simplest ways to prevent these difficulties are to avoid

automated blood pressure measurement devices in patients withmoderate or severe hypertension in pregnancy, or to adopt yoursuggestion of the use of systolic blood pressure to define

hypertension in these circumstances.

6 Cavendish Gardens,Sneyd Park,Bristol BS9 1RQ, UK M. J. QUINN