Occupational exposure to organic solvents has been implicated in the development of "presenile dementia" in several studies. The death certificates of all men aged under 65 dying in England and Wales bearing presenile dementia as cause of death were collected for the years 1 970-9 (n = 557): control death certificates were obtained, matched for age and sex. No significant differences were found between the groups as regards estimated occupational exposure to either organic solvents or lead.Several epidemiological studies, conducted for the most part in Scandinavia, have examined the relation between the occupational exposure to solvents of certain trades and the frequency with which individuals receive disability pensions for neuropsychiatric disorders. Some studies have suggested that the relative risk of receiving such pensions is increased in workers exposed to solvents by a factor of between 2 and 3`1 Others have failed to detect similar increases in solvent workers except for some categories of neurosis.4Reports of groups of individuals attending occupational clinics have suggested that solvent workers in general, and house painters in particular, develop a characteristic syndrome which, with severe disturbances of memory, cognition, and behaviour, is said to be a dementing illness.5 6 A recent case referent study of men receiving diagnoses of dementia failed to find a statistically significant excess of solvent exposed workers compared with matched controls.7After an attempt to perform a case control study of Alzheimer's disease (which failed to recruit satisfactory numbers of subjects) (T D Browne et al, Medichem Conference, Ludwigshaven, 1986) The death certificates record, in addition to general demographic data, the individual's most recent full time paid employment as reported to the Registrar at the time the death was registered.Occupations of both subjects and controls were graded into one of three categories according to probable occupational exposure to organic solvents and to lead. These categories were "no exposure," "possible exposure," and "probable exposure" (see appendix 1).This analysis of occupations was carried out by one of us (HAW) and, independently, by an occupational hygienist. Both were "blind" as to the cause of death on the death certificate. The exposure category was agreed before final allocation. We were particularly interested to see whether painters and decorators were more frequently represented among the cases than the controls since it is this group which has attracted most attention of late. As painters and decorators are likely to have, or to have had, exposure also to lead, which was formerly a common constituent of paints, we have also extended our inquiry to see whether or not there is any suggestion that lead may be associated with presenile dementia. The occupations were categorised with respect to lead exposure in the same way as for solvent exposure (see appendix 2).

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Auguste-Louis Delpech (1818-80) has been remembered principally as the author of the first detailed description of the serious consequences of exposure to carbon disulphide. A close reading of his work suggests that his reputation has been seriously undervalued. The subsequent development of occupational psychiatry, with its emphasis on the distinction between the organic and the functional, may be traced through publications on carbon disulphide. It is argued that a contemporary approach to occupational psychiatry is long overdue.On peut dire que le sulfure asassine; il tue l'homme, il lui fait perdre toute dignite tout respect de soi meme.Patient Monsieur B quoted by Delpech'In the practice of occupational psychiatry one of the central problems is to relate toxic exposures to the development of psychological symptoms. We are even now unable to understand the psychopathological connections between "intoxication" and the phenomena of confusional states whereas for many occupational physicians "functional" disturbances of bodily function are virtually equivalent to deliberate malingering. Psychiatry has always been engaged in controversy to such an extent that historical arguments are forgotten and lessons once learnt must be relearnt.The quite opposing views of Delpech and Charcot that form the basis of this paper are expressed even now in discussions of the relative importance of "organic" and functional factors in the aetiology of occupational disease.Charcot is well known as one of the major figures in the development of neurology whereas Delpech is remembered, if at all, for his work on the adverse effects of carbon disulphide.

Demographics 547 patients; median age (59-62 y) and ECOG 0-1 status (90-97%) similar across the groups (Table 1). Studies with P±R included female patients only (except for 1 male), whereas male patients were the majority in the studies with CPR or CP (68-72%). All patients in P or PR had received prior chemo but only 26% in CP and 40% in CPR. Table 1. Demographics Data (Safety Population) Serious TEAEs considered to be treatment-related by the Investigator are presented in Table 3. Fever, nausea, and vomiting were the only events reported in >1 patient.