analyses of chromosomal banding-patterns


in progress.

Dr Martin R. Klemperer referred this patient for cytogenetic Carol Goodman and Linda Osowski gave valuable studies. technical assistance.

This work was supported in part from the National Cancer Institute. University of Rochester and Monroe Community Hospital, Rochester, N.Y. 14603, U.S.A.


research grant CA-14876


primarily caused by dietary factors. It can be induced experimentally by diets high in carbohydrate but low in protein and fat, and the incidence can also be influenced by environmental factors such as fasting, temperature, and stress. The incidence of the disorder can be reduced by increasing fat and protein levels in the diet, and the disease can be totally prevented by increasing the dietary levels of biotin. However, classical symptoms of biotin deficiency are not observed in the affected birds. Hepatic gluconeogenesis activity is severely depressed in F.L.K.S., but recovery to almost normal levels is obtained by biotin both in vivo and in vitro. IS In both conditions hypoglycsemia is thought to be an important factor in causing death. In view of the established role of biotin in gluconeogenesis and its success in preventing the avian disease, some consideration could be given to the role of dietary cofactors in the treatment and prevention of Reye’s syndrome. In any event, F.L.K.S. may be a suitable model for Reye’s syndrome, whether the latter has a primary nutritional cause or results from the interference of other aetiological agents in a similar metabolic pathway.


REYE’S SYNDROME OF CHILDREN AND THE FATTY-LIVER-AND-KIDNEY SYNDROME OF CHICKENS SIR,-It has been brought to our attention (Prof. J. B. Cavanagh, personal communication) that Reye’s syndrome (encephalopathy and fatty degeneration of the viscera) has many features in common with a condition we are studying in the fowl called the fatty-liver-and-kidney syndrome (F.L.K.S.). Reye’s disease occurs sporadically in many countries, and it is reported to be a leading cause of childhood deaths in Thailand.l Its aetiology is obscure and its pathogenesis poorly understood.2,3 It has been suggested3 that an understanding of this disorder would be aided by further study in animals. F.L.K.S., as a naturally occurring disease which is also experimentally reproducible, may provide a model for the human disorder. Various papers on F.L.K.S. deal with pathology,4-7 biochemistry,8-1o

experimental induction,11.12 and prevention. 13. 14 Both diseases affect the young, causing acute disturbances of consciousness, including coma; the mortality-rate is high. In both there is striking hypoglycaemia, raised blood free-fatty-acid and pyruvate levels, reduced hepatic glycogen, and excessive accumulation of lipid (mainly triglyceride) in the liver, proximal tubules of the kidneys, and myocardium (usually unaccompanied by cellular degeneration or inflammatory reactions). No specific


Agricultural Research Council’s Poultry Research Centre, King’s Buildings, West Mains Road, EH9 3JS.



SIR,-Most of us are concerned with the platelet in blood, but there are no reports about the platelet in urine. One of us (N. K.) has examined urinary sediment from normal and sick persons and has observed a small body

infective or toxic agent has been identified in either the human or the avian disease. There are, however, dissimilarities. Cerebral oedema, which occurs in Reye’s syndrome, is not seen in F.L.K.S. although an unusual deposition of lipid involves the astrocytes. Dyspnoea and pulmonary congestion are also features of Reye’s syndrome which do not occur in F.L.K.S. Serum-aspartate-aminotransferase levels are raised in Reye’s syndrome; this has not been tested in F.L.K.S., but in affected birds isocitric dehydrogenase, leucine aminopeptidase, and cholinesterase levels are within normal limits. Most investigators agree that Reye’s syndrome is a clinical and pathophysiological entity, but the suspected causes are multiple and varied, as indicated by the different virus diseases and agents, such as mycotoxins, which have been associated with it. No prodromal illness occurs in F.L.K.S., which has been found to be a metabolic disorder 1. Olson, L., Bourgeois, C. H., Cotton, R. B., Harikul, S., Grossman, R. A., Smith, T. J. Pediatrics, Springfield, 1971, 47, 707. 2. Schubert, W. K., Partin, J. C., Partin, J. S. Progr. Liver Dis. 1972, 4, 489. 3. Mowat, A. P. Archs Dis. Childh. 1973, 48, 411. 4. Wight, P. A. L., Siller, W. G. Res. vet. Sci. (in the press). 5. Siller, W. G., Wight, P. A. L. ibid. 6. Wight, P. A. L. Neuropath. appl. Neurobiol. (in the press). 7. Wight, P. A. L. J. comp. Path. Ther. (in the press). 8. Whitehead, C. C. Res. vet. Sci. 1975, 18, 32. 9. Evans, A. J., Bannister, D. W., Whitehead, C. C. ibid. p. 26. 10. Bannister, D. W., Evans, A. J., Whitehead, C. C. ibid. p. 149. 11. Whitehead, C. C., Blair, R. ibid. 1974, 17, 86. 12. Whitehead, C. C., Bannister, D. W., Blair, R., Evans, A. J. ibid. p. 222. 13. Whitehead, C. C., Blair, R., Bannister, D. W., Evans, A. J., Jones, R. M. ibid. (in the press). 14. Payne, C. G., Gilchrist, P., Pearson, J. A., Hemsley, L. A. Br. Poult. Sci. 1974, 15, 489.

Scanning electron microscopic findings The upper small



of urine sediment.

dendritic, the lower is discoid.

( x 2500.) __________



platelet in size,

appearance, and



We have compared the platelet-like body in urine with normal platelets in blood and also with platelets in normal urine supernatant to which had been added platelet-rich 15. Bannister, D. W. Comp. Biochem. Physiol. (in the press).


plasma (P.R.P.) anticoagulated by ethylenediamine tetraacetic acid (E.D.T.A.). With Giemsa staining, azure granules appeared in the pale-violet cytoplasm of the small bodies. Phase microscopy showed that the bodies were spherical or spheroid in shape with an irregular and pitted surface, and sometimes having small projections (dendritic shape). Most of the platelets in blood and those added to urine were spheres or spheroids with projections. On scanning electron microscopy, the small bodies were discshaped with an irregular and pitted surface (average diameter of 3-8 ), spherical with a smooth surface (average diameter of 2-7 .), or dendritic (as in the accompanying figure). Most of the platelets added to urine were spherical with a smooth surface or dendritic with a distorted surface, although some remained as discs, as described by Larrimer et al.1 Samples of P.R.p.-urine were left at room-temperature and at 4°C, respectively. On Giemsa staining, the platelets in urine after one week did not stain so well as those in the fresh preparation; but the number of platelets in urine stored for one week did not decrease. Further investigation is required, but we suggest that these small bodies in urine are platelets. We thank Mr T. Fujiwara, Keio University, and Mr T. Mizokami, Nishinippori Clinic, for help.

Tokyo Electric Power Hospital, Shinanomachi, Shinjuku-ku, Tokyo. Nishinippori Clinic, 5-24-7, Nishinippori, Arakawa-ku, Tokyo, Japan.




SiR,—Surgical textbooks 2-4 recommend the use of metal cannulse, three-way stopcocks, and 20-50 ml. syringes for aspiration of pleural effusion. A number of unnecessary problems arise when these implements are employed, including pneumothorax and jamming of the stopcock. The procedure is exhausting not only to the already dyspnoeic patient but also to the doctor. The patient has to restrict respiratory effort for fear of trauma to the lung or diaphragm with the sharp needle. All these disadvantages and complications are lessened, if not eliminated, by a simple method whereby a plastic intravenous cannula (e.g., Braunula size 1) is connected to an intravenous giving-set, for drainage by a one-way system controlled by the plastic valve supplied with the giving-set. The cannula is inserted through a small nick in the locally anaesthetised area selected to drain the maximum amount of pleural effusion. The patient holds his breath for only a second or two while the metal introducer is removed and the giving-set connected. The connection between the giving-set and the cannula is certainly more secure than in the previous method. The patient can lie back comfortably at 45 degrees, breathe, and even cough without fear of injury. The pleural effusion drains freely into a receiver on the floor; its rate of flow is easily controlled and any air that may enter the tubing is prevented from reaching the pleural cavity by simply closing the valve. At the end of the procedure the plastic tubing is cut short for injection of any chemotherapeutic agent, still leaving the valve in position to stop any possible air entry. In a series of over sixty aspirations of malignant pleural effusion with the above technique the drainage was more complete, simple, comfortable than with the standard method and not a single case of pneumothorax or any other 1.

2. 3. 4.

Larrimer, N. R., Balcerzak, S. P., Metz, E. N., Lee, R. E. Am. J. med. Sci. 1970, 259, 242. Kyle, J. Pye’s Surgical Handicraft; p. 307. Bristol, 1969. Sabiston, D. C. Jr., Davis-Christopher Textbook of Surgery; p. 1815. Philadelphia, 1972. Kyle, D. Minor Surgery; p. 129. London, 1968.

serious rays

noted. In all the taken after each procedure.



57 Cromwell Road, London SW7 2ED.




chest X-



SiR,-Dr Gupta (March 15, p. 641) discounts completely the arrhythmogenic role of the sympathetic nervous system (s.N.s.) and questions the relevance of the proven of catecholamines in the blood and urine after myocardial infarction (A.M.I.) to production of arrhythmias in man. This requires comment. Lown’s group1 showed that sympathetic stimulation lowers ventricular fibrillation threshold (v.F.T.)-i.e., it increases cardiac vulnerability to fibrillation-and they suggested that inappropriate sympathetic discharge may induce ventricular fibrillation (v.F.) and, therefore, sudden death. Dr Gupta considers these conclusions unwarranted because the study was made in dogs and because electrical stimulation was used to provide sympathetic discharge. Lown’s group showed also that V.F.T. is reduced by hypothalamic stimulation and that this effect is suppressed by beta-blockers 2; in addition, they showed that cardiac vulnerability to v.F. is increased when dogs are placed in a stressful environment3 and conclude: " Thus, intense activity of the central nervous system, whether induced by direct electrical stimulation or by psychological means, can profoundly affect the susceptibility of the heart to fatal arrhythmias" .2 Bilateral stellectomy increases V.F.T.4 Striking changes in v.F.T. have also been obtained by unilateral stellate-ganglion ablation or blockade: removal of the right stellate ganglion lowers V.F.T. (48%), whereas removal of the left increases v.F.T. (72%).5 These profound changes in cardiac vulnerability to v.F. are the result of unilateral withdrawal of spontaneous cardiac sympathetic activity and do not depend on electrical stimulation. Similarly, blockade of the right stellate ganglion increases the arrhythmias associated with coronary-6 artery occlusion, while blockade of the left reduces them. Dr Gupta reports a study where adrenaline infusion was used to produce lung oedema and where cardiac arrhythmias were not mentioned; since that paper deals with lung cedema, the lack of description of arrhythmias does not rule out that they occurred. He reports also an anecdotal suicidal attempt with adrenaline which did not produce arrhythmias (continuous E.c.G. monitoring ?). He uses these data against the role of catecholamines in arrhythmia production, but he does not quote papers reporting arrhythmias produced by catecholamine infusion.7.8 The major point, however, is that Dr Gupta seems to be unaware of the fact that stimulation of cardiac sympathetic nerves increases the temporal dispersion of excitability recovery in ventricular muscle (a factor known to favour arrhythmias 9), and that administration of catecholamines decreases it.lo In fact, stimulation of cardiac nerves increases cardiac vulnerability to v.F., whereas catecholamine infusion decreases it (after about 3 minutes of infusion, when the substance




Verrier, R. L., Thompson, P. L., Lown, B. Cardiovasc. Res. 1974, 8, 602.

Verrier, R. L., Calvert, A., Lown, B. Am. J. Physiol. 1975, 228, 923. Lown, B., Verrier, R., Corbalan, R. Science, 1973, 182, 834. Kliks, B. R., Burgess, M. J., Abildskov, J. A. Circulation, 1972, 46, 115. 5. Schwartz, P. J., Snebold, N. G., Brown, A. M. Am. J. Cardiol. 1975, 35, 169. 6. Schwartz, P. J., Stone, H. L., Brown, A. M. Circulation, 1974, 50, 204. 7. Lepeschkin, E. Cardiologia, 1950, 16, 278. 8. Szakacs, J. E., Mehlman, B. Am. J. Cardiol. 1960, 5, 619.

2. 3. 4.

9. Han, J., Goel, B. G. Archs intern. Med. 1972, 129, 749. 10. Han, J., Moe, G. K. Circulation Res. 1964, 14, 44.

Letter: Platelets in human urine?

1339 analyses of chromosomal banding-patterns are in progress. Dr Martin R. Klemperer referred this patient for cytogenetic Carol Goodman and Lind...
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