lonomeric cement and aluminium encephalopathy

design and analysis followed WHO recommendations (1989). The number of sheep used in the estimation of The

cumulative exposure was the average size of the farmer’s flock over the past years rather than the total number of sheep dipped. The Pearson correlation between the product that we calculated and age was only about 0- 11. The average ages of the farmers and controls did differ but age was included as a covariate in the analysis. All factors (our table 1) that exhibited significant differences between farmers and controls were included in the analysis. Sheep farmers were studied at a time when exposure to organophosphates was likely to be low (as confirmed by urinary metabolites). This was at least 2 months after dipping and when sheep handling was limited (eg, before lambing). Time of testing (morning or evening) was controlled for, as was level of computer experience. There was no indication that farmers in the three areas performed differently; nor were there any differences by area in responses to the General Health Questionnaire. If stress from the Chernobyl incident had affected two of the three areas we would expect that to be reflected in the results. Does Watts have evidence for an association between Chernobyl effects and chronic stress? The tests we applied are sensitive indicators of effects on cognitive functioning. Such effects may be present in the absence of symptoms. Davies also comments on the consequences of the changes identified but we feel that these changes would be unlikely to have noticeable effects on everyday functioning. We cannot say whether those under treatment for psychiatric disorders elected out of the study but if any such individuals had been included this would have increased the significance of the results. Given the current climate of this debate, however, it is equally possible that some individuals on such treatment might elect themselves in. The high exclusion rate among farmers was mainly due to lack of exposure (eg, they were hobby farmers who owned very few sheep) and we could not have known this in advance from the Wool Marketing Board lists of sheep farmers. 13 farmers were excluded initially because of nervous system disease (epilepsy) or the risk of it (diabetes) or previous head injury, and a further 3 later found to have an alcohol problem were excluded from the analysis. 8 controls were initially excluded because of head injury, and 1 was excluded from the analysis because of self-reported regular drug use. The control group’s self-reported alcohol consumption was higher than that of the farmers. Only 1 person (a control) had to be excluded because of alcohol consumption on the day of testing. None of our farmers had experienced acute poisoning. Such incidents are rare if hospital admission is taken as the definition of "acute incident". The full report’ shows a low incidence of symptom reporting in this group of farmers immediately after sheep dipping. Also, in answer to O’Brien and colleagues, we note that questions on neurotoxicant exposure as a result of previous occupation, gardening, and other hobbies resulted in the exclusion of 13 controls. Urinary metabolites indicated that their exposure was similar to that of populations with no specific exposure and to that of the farmers at the time of testing.5 Those farmers had taken part in an earlier symptom-reporting stage of the study

immediately

after

sheep dipping. Urinary analysis

at

that

stage confirmed significant exposure. Media attention and the political climate surrounding an issue may well affect participation rates and responses. We have a special interest in the psychosocial aspects of symptom reporting and these factors further complicate the

investigation of occupational and environmental hazards. Our attitude questionnaire indicated

that those who viewed organophosphates negatively reported more symptoms immediately after dipping and more symptoms on the General Health Questionnaire, but attitudes and test performance were not related. *A

Spurgeon,

Ian Calvert, L S

Institute of

1

2

3

4

5

J M Harrington Birmingham,

Levy,

Occupational Health, University Birmingham B15 2TT, UK

of

Stephens R, Spurgeon A, Beach J, et al. An investigation into the possible chronic neuropsychological and neurological effects of occupational exposure to organophosphates in sheep farmers (HSE Contract Res Rep no 74/1995). London: HSE Books, 1995. Daniell W, Stebbins A, O’Donnell J, Hortsman SW, Rosenstock L. Neuropsychological performance and solvent exposure among car body repair shop workers. Br J Indust Med 1993; 50: 368-77. Spurgeon A, Glass DC, Calvert IA, Cunningham Hill M. Investigation of dose related neurobehavioural effects in paintmakers exposed to low levels of solvents. Occ Env Med 1994; 51: 626-30. Stollery BT, Broadbent DE, Banks HA, Lee WR. Short term prospective study of cognitive functioning in lead workers. Br J Indust Med 1991; 48: 739-49. Berry HF, Nutley BP. Dialkylphosphate concentrations in the urine of workers exposed to organophosphate-based sheep dips (HSE Publ IR/L/OT/95/5). London: HSE, 1995.

lonomeric cement and aluminium

encephalopathy SiR-Renard and

colleagues’ and Hantson and colleagues (Dec 10, p 1647) report 4 cases of subacute aluminium myoclonic encephalopathy that occurred after bone reconstruction with an aluminium-containing biomaterial. We have analysed in a rabbit model the role of aluminium in neurosurgical procedures. A craniotomy in the left frontal region was done with the dura mater either incised or left intact. The bony defect was reconstructed with the ionomeric cement (supplied by Ionos GmbH & Co KG, Seefeld, Germany) without any further protection to the soft tissue underneath. After 2 and 6 weeks the concentration of aluminium was determined in cerebrospinal fluid (CSF) and plasma as well as in the cortical tissue underneath the operation sites and from the contralateral occipital region. Histological evaluation of the brain tissue was done. Overall, there was no increase in aluminium. In most cases the concentration of aluminium in plasma as well as in CSF was below the detection limit whether the dura was left intact or showed an incision without reconstruction. An increase was shown in 1 control and 1 test animal (2 weeks, dura incised).* For both these animals no neurological signs, seizures, coma, or behavioural deficits were registered. 1 animal died with signs of distress without any correlation with aluminium concentrations. No pathological changes were found in central nervous system (CNS), liver, heart, or kidneys. Only those animals with direct contact of the bone cement to the cortex showed signs of necrosis of the cortex and subcortical white matter underneath the operation sites.2 The cerebral parenchyma of the remaining rabbits did not show any inflammatory changes, hypoxic-ischaemic neuronal damage, or necrotic lesions. We have found argyrophilic aluminum-containing inclusions in the choroid plexus, glial cells, and neuronal cytoplasm of the CNS in long-term haemodialysis.3 Contrary to Renard and colleagues’ findings, we did not find extensive necrotic lesions to be a feature of dialysis encephalopathy. Published work shows that only high aluminium concentrations of above 200 )g/L plasma are associated with

epidemiological

*Contact the authors for detailed information.

1633

encephalopathy, and only if these high concentrations are maintained. aluminium Thus, concentrations of 170-180 jg/L plasma are regarded as a critical level for working people exposed to aluminiumcontaining material. Between October, 1988, and May, 1994, 99 patients with bony defects in the skull base underwent surgery and use of ionomeric cement. The patients had defects of the anterior skull base (25), lateral skull base (25), frontal bone (17), nasal slope (6), hypotympanum (jugular bulb) (5), orbital floor (3), calvaria (2), alveolar rim (2), orbital roof (2), and petrous apex (translabyrinthine acoustic neuroma resection) (12). It was ensured that the implantation bed had no contact with the CSF space. This was achieved by reconstructing the dura with preserved dura and sealing with fibrin glue. The bony gaps, measuring 5-8 cm, were filled with freshly mixed cement. Alternatively prefabricated cement implants were neatly adapted to the bony rim with cement. No adverse cerebral or neurological reactions developed in any of these cases. Our preclinical and clinical data do not show a substantial increase of aluminium in CSF/cerebral tissue or any detrimental clinical consequences or damage of cerebral parenchyma after usual closure of the dura mater.9°’ dialysis

NT=not tested (no lymphocytes available), NT*=not tested (no sample was found once positive and once negative by NASBA.

Table: Results of

serum

available). tThls

virological investigations

observed at the beginning of November, 1993 (6th month after accident). No lymph nodes were found on physical examination. HIV serology had been negative at the 3rd and 6th months after the accident but it was positive at the 8th month. The first positive western blot showed a full pattern of infection. Serum p24 antigen remained negative on all studied samples. The qualitative HIV-RNA NASBA assay’ was positive for the first time on the plasma sample collected during symptoms of acute infection. The subsequent plasma sample corresponding to the appearance of HIV antibodies was found once positive and once negative, suggesting a low HIV-RNA level. Later samples were all clearly NASBA positive. HIV could not be isolated by culture on the successive blood samples, even on 1 the more recent sample, collected year after seroconversion. The table gives results of the virological investigations (some were done retrospectively on frozen were

*E Reusche, J Rohwer, W Forth, J Helms, G Geyer *institute of Pathology, Medical Univesity, D-23538 Lubeck, Germany; Institute of Legal Medicine, Medical University, Lubeck; Walter-Straub-Institute for Pharmacology and Toxicology, Munich; Julius-Maximilians-University, ENT Department, Wurzburg; and Städtisches Krankenhaus, ENT Department, Solingen

1 2

3

4

5

Renard JL, Felten D, Béquet D. Post-otoneurosurgery aluminium encephalopathy. Lancet 1994; 344: 63-64. Geyer G, Wiedenmann M, Borrmann I. Ionomerzement (Ionocem) als Knochenersatzmaterial in der plastisch-rekonstruktiven Schädelchirurgie-tierexperimentelle Untersuchungen und klinische Ergebnisse. German Society Plastic Reconstructive Surgery, 30th annual meeting, Berlin, 1992. Reusche E, Seydel U. Dialysis-associated encephalopathy: light and electron microscopic morphology and topography with evidence of aluminium by laser microprobe mass analysis. Acta Neuropathol 1993; 86: 249-58. Helms J, Geyer G. Alloplastic material in skull base reconstruction. In: Dekhar LN, Janecka IP. Surgery of cranial base tumors. New York: Raven Press, 1993; 461-69. Helms J, Geyer G. Closure of the petrous apex of the temporal bone with the ionomeric cement following translabyrinthme removal of an acoustic neuroma. J Laryngol Otol 1994; 108: 202-05.

Time to HIV seroconversion after needlestick

injury SiR-The exact duration of the period between first contact with HIV and the appearance of specific antibodies varies and remains a subject of controversy. Seroconversion usually takes place 2-3 months after HIV infection. However, the possibility remains of the existence of a subpopulation of HIV-infected individuals with a window going beyond 6 months. We report a case of HIV infection following a needlestick injury in which seroconversion was observed beyond the 6th month after the accident. A 47-year-old woman of Algerian origin was accidentally pricked by a needle on May 10, 1993, at the clinic where she worked as a cleaner. Serological tests in accordance with French law were done at the time of the accident and in the 3rd and 6th months afterwards. No zidovudine prophylaxis was prescribed at the time of the accident. She had no personal risk factors for HIV infection, and no at-risk circumstances between the accident and the diagnosis of HIV infection. Symptoms of possible acute primary infection 1634

samples). This case indicates that the possibility exists of a serologically silent window going beyond 6 months (in our patient, this period was between 6 and 8 months). Such delayed seroconversion could be linked to a weak viral inoculum or to the percutaneous mode of contamination, which may be responsible for a low diffusion to the lymphoid system. Indeed, the duration of the window varies according to the type of contamination. In a few welldocumented cases, the window was 35-50 days in cases of sexual transmission,2,3 and as few as 26 days when infection occurred through organ transplantation.4 Delayed seroconversion could also be linked to an attenuated strain of HIV; indeed, no isolation of the virus was obtained despite six attempts. In our patient, p24 antigen was not detected before seroconversion on studied samples, but this marker is present during only a fraction of the window period.’ However, the evolution of HIV RNA in our patient corresponds to what is currently observed in HIV infection: high levels of plasma HIV RNA, often exceeding those found in patients with AIDS, are evident in HIV-infected people before seroconversion; at the time of the immune response a dramatic drop of circulating virus is observed, and then HIV RNA becomes nearly undetectable. Subsequently, viral RNA becomes clearly detectable again. This sequence was observed in our patient. The possibility of a serologically silent window of more than 6 months may have public health consequences. The underestimation of the diagnosis of HIV infection may