List of Illustrations ix Acknowledgments xi References Index Contents vii For their comments on early versions of the arguments presented here, I thank Professor Mary B. Hesse and Professor Nicholas Jardine, University of Cambridge, and Professor James R. Brown, University of Toronto. They do not entirely agree with my views, as will be obvious from their own writings. I am grateful to two anonymous referees of Cornell University Press for their perceptive comments on the penultimate draft. Lastly, I thank my colleagues and friends at the University of Leiden for providing the pleasant environment in which this work was completed. Some material in this book is developed from the following publica

The most promising way to regard thought experiment is as a species of experiment, alongside concrete experiment. Of the authors who take this view, many portray thought experiment as possessing evidential significance intrinsically. In contrast, concrete experiment is nowadays most convincingly portrayed as acquiring evidential significance in a particular area of science at a particular time in consequence of the persuasive efforts of scientists. I argue that the claim that thought experiment possesses evidential significance intrinsically is contradicted by the history of science. Thought experiment, like concrete experiment, has evidential significance only where particular assumptions-such as the Galilean doctrine of phenomena-are taken to hold; under alternative premises, in themselves equally defensible, thought experiment is evidentially inert. Copyright 0 1996 Elsevier Science Ltd.

No abstract

In a prospective study of 26 premature infants, 5 ,l microdrops were compared with standard 26 ul eye drops of cyclopentolate 0-5% and phenylephrine 2 5%. There was no statistical difference in pupil dilatation. The 5 gl microdrops have potentially fewer adverse effects in premature infants. (BrJf Ophthalmol 1993; 77: 364-365) Systemic toxicity from DiscussionThe volume of an eye drop from a minim is 26 /u16 which is greatly in excess of the adult precorneal tear film volume of 7 ul.7 Eighty per cent of standard drops may be lost in the first 15-30 seconds via the nasolacrimal duct, conjunctival blood vessels, or spillage onto the skin. Systemic absorption is directly into the circulation from the conjunctival and nasal mucosa without first pass metabolism in the liver. Therefore systemically absorbed eye drops are more like intravenous agents than oral ones.7There was no statistically significant difference in pupil dilatation in this study between the smaller 5 ul drop size and the conventional 26 ul drop size. Equal pupil dilatation has been demonstrated with 8 ,ul and 30 ul drops of phenylephrine in neonates but the pupil size was only 4-86 mm and 4-57 mm respectively.8 The pupil diameter was larger in this study which is compatible with the results of Carpel and Kalina who showed there was an additional effect in premature infants when cyclopentolate was added.9 In adults reduction in drop size of phenylephrine 10% and tropicamide 1% produces adequate mydriasis.6Brown et al have shown that drop size can be reduced by designing a bottle with a narrower outlet.'0 The systemic absorption is less with a smaller than a larger drop volume.8 Infants in particular may be more likely to absorb eye drops systemically as the tear volume is small and the drops are instilled supine so that spillage onto the skin may be less. " The risk oftoxicity may also be increased because of low body mass and the immaturity of the cardiovascular and nervous systems.4 Cyclopentolate in adults and children may cause psychosis, behavioural disturbance, ataxia, agitation, fits, and gastrointestinal upset.'2 Preterm twins developed gastrointestinal side effects from cyclopentolate 1%, and abdominal distension and increased gastric aspirate was reported in 50 preterm infants examined for retinopathy of prematurity.512 There are many reports of cardiovascular adverse effects from phenylephrine.' 2 Raised blood pressure has been observed in preterm infants after dilatation with 2 5% phenylephrine and this potentially increases the risk of intraventricular haemorrhage.4The risk of adverse systemic effects from eye drops is well recognised and as more and more premature babies are being examined it would be better medical practice not to use over five times more medication than is required.

No abstract