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There is something faintly absurd about arguing for the intellectual respectability of a discipline that can lay claim to a pedigree of almost two centuries and a distinguished list of practitioners spanning five continents. Yet contributors to the first Critical Cluster took up the challenge and set forth with vigour serious arguments for the vitality, adaptability and potential of the discipline. Who had claimed the contrary? The Guest Editor had been scrupulous only to pose a hypothetical question. Reading the responses with the benefit of a conspectus denied to the individual contributors, I am struck by their willingness and determination to answer in intellectual terms a question that has at least as many political and educational dimensions. Whether market forces and governmental philistinism (or at least indifference) have brought Historical Romance Linguistics to its knees in many of our universities is a question that certainly deserves debate, especially if we believe that we can, collectively, do something about it. Only a minority of the contributions confront these issues, and then after establishing intellectual credentials. I shall try to complement the minority. Debates on the supposed crisis in Romance linguistics and its expected demise are not new. Malkiel diagnosed a period of self-doubt in the period 1900-1930, partly ascribed to an arid Verschulung (1972: 856-58); Posner reported an eclipse and crisis of confidence in the 1950s and 1960s (1970: 412-14); and more recently, anguished debates have been taking place in Germany on the future directions and sustainability of Romanistik (see Kramer 2004, responding to discussion

The variationist paradigm of sociolinguistics launched by Labov has brought about radical revision in the way we view linguistic evolution. This book is the first to systematically apply the insights within French linguistics. This book should be of interest to students and teachers of linguistics, sociolinguistics, French and Romance linguistics, historical and comparative linguistics.

(R)-(-)-benoxaprofen is stereospecifically inverted to the (S)-(+)-enantiomer by rats and humans. The rate of inversion is much faster in rats (t 1/2 ca. 2.5 h) than in humans (t 1/2 108 h). Inversion in rats apparently does not occur in the liver, but can be brought about in vitro by an everted intestinal sac preparation, suggesting that the transformation takes place while passing through the gut wall.

1. The absorption, distribution, metabolism and excretion of benoxaprofen, a novel anti-inflammatory compound, has been studied in the dog, mouse, rat, rabbit, rhesus monkey and man. 2. Benoxaprofen was well absorbed after oral administration of doses of 1 to 10 mg/kg in all six species. Only unchanged drug was detected in plasma. It was extensively bound to plasma proteins, the highest binding occurring in man (99.8%) and rhesus monkey (99.6%). 3. Species differences were observed in the plasma elimination half-life, the longest being in man (33 h). The rat and mouse also had high values (28 and 24 h respectively) whereas in the other species, values were less than 13 h. 4. After an oral dose of [14C]benoxaprofen (20 mg/kg) to female rats, tissue concn. was highest in liver, kidney, lungs, adrenals and ovaries. Tissue distribution in the pregnant rat was identical to the normal female. The compound was found in the foetus but at a concn. lower than in all maternal organs. 5. There was a marked species difference in the route of excretion. In man, rhesus monkey and rabbit, excretion in the urine was a major route, whilst biliary--faecal excretion was the only effective route in the rat and dog. 6. No major metabolic transformation of benoxaprofen was observed. Man and dog excreted the compound predominantly as the ester glucuronide whereas the rat, mouse, rabbit and rhesus monkey excreted a large proportion of the dose unchanged.

It is widely believed, in Spain and abroad, that the passive is rarely used in standard Castilian. Alonso del Rio, for instance, tells us that ‘en nuestro idioma se hace un empleo muy limitado de la voz pasiva’.Seco has, ‘La voz pasiva refleja es en espanol mucho mas frecuente que la formada con el verbo ser, que, por su parte, es una construccion practicamente rara’. Ramsey considers that the formal passive is not much used ‘because of the number of equivalent constructions’. Harmer and Norton quote the Academy and suggest, ‘The passive is often replaced by the reflexive’.

1. The absorption, metabolism and excretion of isamoxole, (2-methyl-N-butyl-N-(4-methyloxazol-2-yl)propanamide), a compound with anti-allergy properties, has been studied in the rat and guinea-pig. 2. The compound was well-absorbed by both species after oral doses of 50 to 150 mg/kg. It underwent extensive first-pass metabolism in the liver, and was excreted as a mixture of metabolites, predominantly in the urine, within 48 h. 3. Three major routes of metabolism were involved, namely deacylation, oxidative ring scission and alkyl oxidation. 4. A major plasma and urine metabolite was 1-butyl-3-(1-carboxyethyl)urea, and this was accompanied by low levels of its cyclized product 3-butyl-5-methylhydantoin.

The serum protein binding, uptake by parasites and mode of action of 2-(4'-carboxystyryl)-5-nitro-1-vinylimidazole (I) were investigated. Compound I was strongly bound to serum proteins in all species, especially the rat. The albumin of this species appeared to possess a single high-affinity site not present in mouse or dog albumin. Only unbound I was taken up by Trichomonas vaginalis . In vitro , a short exposure of Trichomonas vaginalis to levels of I above 5 μg/ml led to their subsequent death even after transfer to fresh medium. At low concentrations, I was degraded by the organisms which then recovered. Compound I reacted in vitro with thiol compounds and enzymes. It inactivated three glycolytic enzymes in intact Trichomonas vaginalis and Trypanosoma rhodesiense and caused a marked depletion of intracellular ATP before any effects on motility were apparent.

A high proportion of the acidic anti-inflammatory compound benoxaprofen is bound to the plasma proteins of humans and rats (99.8 and 99.3 per cent respectively). The binding did not vary significantly up to total levels of about 120 μg/ml in human plasma or about 40 μg/ml in rat plasma. Above these levels the proportion bound decreased. At 50 μg/ml, more than 90 per cent of benoxaprofen was associated with the albumin fraction of normal human serum. At higher levels, this binding site became saturated and non-specific binding to all proteins appeared to occur. There was no difference between normal and arthritic subjects. In normal rat serum, there was much less bound to albumin. Total binding was reduced in adjuvant arthritic rats. due to decreased binding to α and β 1 globulins. At plasma levels in the range required for therapeutic activity, benoxaprofen did not displace warfarin, salicylate, prednisolone or dexamethasone from their binding to human plasma proteins. In contrast, therapeutic levels of phenylbutazone displaced warfarin.