Discovery and occurrence of the fumonisins: a historical perspective.

This article describes the events leading to the discovery of the fumonisins in South Africa in 1988 and highlights the first 10 years (1988-1998) of fumonisin research. The predominant fungus isolated from moldy corn implicated in a field outbreak of equine leukoencephalomalacia (ELEM) in South Africa in 1970 was Fusarium verticillioides (F. moniliforme). This fungus was also prevalent in moldy home-grown corn consumed by people in high-incidence areas of esophageal cancer (EC) in the Transkei region of South Africa. Culture material on corn of F. verticillioides strain MRC 826, which was isolated from moldy corn in Transkei, was shown to cause ELEM in horses, porcine pulmonary edema (PPE) syndrome in pigs, and liver cancer in rats. A short-term cancer initiation/promotion assay in rat liver was used to purify the carcinogen(s) in the culture material. These efforts finally met with success when fumonisins B1 and B2 novel mycotoxins with cancer-promoting activity in rat liver, were isolated from culture material of F. verticillioides MRC 826 at the Programme on Mycotoxins and Experimental Carcinogenesis of the Medical Research Council in Tygerberg, South Africa. Following the elucidation of the chemical structure of the fumonisins, these carcinogenic mycotoxins were shown to occur naturally in moldy corn in Transkei. Shortly thereafter, high levels of fumonisins in the 1989 U.S. corn crop resulted in large-scale field outbreaks of ELEM and PPE in horses and pigs, respectively, in the United States. Subsequently the fumonisins were found to occur naturally in corn worldwide, including corn consumed as the staple diet by people at high risk for EC in Transkei and China. These findings, together with the fact that the fumonisins cause field outbreaks of mycotoxicoses in animals, are carcinogenic in rats, and disrupt sphingolipid metabolism, have resulted in much worldwide interest in these compounds during the first 10 years after the discovery of the fumonisins in 1988.

[Neurology in Paris hospitals, particularly the Salpêtrière before Charcot: Rostan on brain softening]. / La neurologie à l'Assistance Publique et en particulier à la Salpêtrière avant Charcot. L'exemple de Rostan et du ramollissement cérébral.

In the beginning of the 19th century, many studies were devoted to the diseases of the nervous system in France, long before the work of Charcot. The researches of Léon Rostan on the cerebral softening (1819, 1823) were based on the anatomoclinic method developed by the School of Paris whose most famous representatives were Corvisart and Laennec for the study of heart and lung diseases. The researches of Rostan were performed in the Salpêtrière hospital which was, at this time, an hospice for old women. Rostan was appointed Inspector of the Health service in the Salpêtrière hospital in 1812 then Head of a department in 1818. He was 28 year old when he published his book "Researches on the cerebral softening" in 1819. Rostan was the first to describe the spontaneous cerebral softening as a special anatomoclinic entity distinct from encephalitis and apoplexy. He compared this entity to the senile gangrene and stated that it was related to the ossification of cerebral arteries. He described the pathologic features of the brain softening and also its clinical symptomatology in opposition to that of apoplexy. The concept of brain softening according to Rostan was harshly fought by the followers of the Broussais's physiological medicine (from Lallemand, 1830 to Calmeil, 1859) who claimed that all brain softenings were due to the inflammation process and thus should be described as encephalitis. In opposite, the ideas of Rostan were accepted and developed by others such as Carswell in England (1835), Abercrombie in Scotland (1836) and Andral in France (1827, 1840). These authors agreed that some type of cerebral softening was related to a disease of the arterial system. Nevertheless, the modern concept of brain softening was not definitively accepted before the description of the thromboembolic mechanisms by Virchow in Germany (1856) with the help of the microscope, and the anatomoclinic studies of Proust, Laborde and Prevost and Cottard in France (1866). The book of Rostan was dedicated to the "Conseil Général des Hospices" which was created in 1801 to unify the administration of the hospitals in Paris and became the "Administration Générale de l'Assistance Publique à Paris" in 1849. One hundred and fifty years after its publication, the work of Léon Rostan was outstanding by its modernity of the form as well as the substance.

[The concept of cerebral lacunae from 1838 to the present]. / Le concept de lacune cérébrale de 1838 à nos jours.

The term lacunae was first used by Dechambre (1838) referring to small cavities developed during the process of resorption within cerebral softenings. Some years later, lacunae was applied by Durand-Fardel (1843) to small cavities located in the basal ganglia and hypothetically attributed to old, healed cerebral softenings. Durand-Fardel (1842, 1854) described "l'état criblé" as many round small holes ("criblures") always containing a patient blood vessel and located in the hemispheric white matter. He believed that "état criblé" was caused by mechanical compression of cerebral tissue related to the dilatation of the blood cerebral vessels during repetitive cerebral congestion. Chronic dementia or delirium were considered as the clinical counterpart of "état criblé". In the second half of the XIXth century, the few reports about lacunae were confusing due to the imprecise use of the terms "lacunae" and "état criblé". Furthermore, some authors described lacunae as sequelae of haemorrhage, others as old softenings or both. In the beginning of the XXth century, the masterly work of P. Marie (1901) established a clear distinction between the "foyers lacunaires de désintégration" and "état criblé" de Durand-Fardel or single perivascular dilatation of one of the lenticulo-striate arteries at its entrance into the lenticular nucleus or post-mortem charges (cerebral porosity, "état de fromage de gruyère"). He described lacunae as small cerebral softenings caused by occlusion of the blood vessels by a "local arteriosclerotic process". However, he also stated that some lacunae containing a patent blood vessel were due to a perivascular space dilatation destroying the adjacent brain parenchyma by a process of "destructive vaginalitis". Marie observed that lacunae were frequently clinically asymptomatic, but "that the hemiplegia of the old people was more often due to cerebral lacunae than to cerebral haemorrhage or softening". During the first half of the XXth century, all the papers devoted to cerebral lacunae were in accordance with the work of P. Marie, developing his own's contradictions. Many authors emphasized the "destructive vaginalitis way" and claimed that lacunae were dilatations of the perivascular spaces. Many other authors developed the "softening way" masterfully illustrated by Fisher who considered lacunae as small deep infarcts caused by a specific pathological process of lipohyalinosis due to arteriolar wall modification by hypertensive disease.(ABSTRACT TRUNCATED AT 400 WORDS)