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1. Wilson, S. A. K. Neurology. London, 1954.2. Hunter, D. The Diseases of Occupations. London, 1955.3. Smith, H. I., Spalding, M. J. K. Lancet, 1959, ii, 1019.4. Aring, C. D. Brain, 1942, 65, 34.5. Geoffroy, H., Slomic, A., Benebadji, M., Pascal, P. Wld Neurol. 1960,
1, 294.6. Burley, B. T. J. Amer. med. Ass. 1932, 98, 298.7. Cavanagh, J. B. J. Neurol. Neurosurg. Psychiat. 1954, 17, 163.
We are very grateful to Prof. H. G. Hers (University of Louvain)for the enzyme determinations on liver biopsy material referred to inthe table. We are further indebted to Prof. E. C. Slater for his
stimulating interest and valuable suggestions.W. C. HÜLSMANN
M.D.Senior Lecturer in Biochemistry
T. L. OEIDemonstrator in Biochemistry
Laboratory of Physiological Chemistry,University of Amsterdam,
Amsterdam, The Netherlands
S. VAN CREVELDM.D.
Professor of PædiatricsPediatric Clinic,
University of Amsterdam
SENSORY TERMINAL DEGENERATION INORTHO-CRESYL PHOSPHATE POISONINGTHE paralysis caused by o-cresyl phosphate in man is
clinically thought to be motor in type.1-3 But directevidence of this is scanty; and, since there is little muscularwasting in the first month, it is likely that factors otherthan motor-nerve degeneration account for the motorweakness. Among these are spinal-tract changes; but thedegree to which these operate in relatively minor cases ofpoisoning is unknown, because necropsy material isavailable only from those that are badly affected.4 Clinicalevidence of sensory disturbance was seen in some cases inthe recent Moroccan outbreak; thus transitory cutaneous
Fig. 1ņMuscle spindle in flexor digitorum brevis stained withsudan-black B to show entering myelinated nerve fibre andannulospiral ending. ( x 165.)
sensory changes were noted 5 in Morocco as in previousoutbreaks. e
In the present study of the effects of tri-o-cresylphosphate on cats, functional disturbances very closelysimilar to those met with in man were produced.Muscular wasting was very slight, but ataxia (sometimes
with transient high stepping gait) and motor weakness (withfoot drop) were regularly found. The hind limbs were alwaysmore affected than the forelimbs. There was the characteristicdelay of about two weeks after one or two subcutaneousinjections of 0-25-0-5 ml. per kg., and thereafter degeneration ofnerve fibres coincided with the onset of symptoms just as itdoes in the hen.7 As in poisoned humans and chickens, fibresof fasciculus gracilis and corticospinal tracts in regions mostdistal from their parent neurones were constantly damaged,but the numbers of degenerating fibres in each tract wasrelativelv small.
Fig. 2-Muscle spindle as in fig. 1 but from cat 4 weeks after onsetof paralysis due to T.O.C.P. ( x 165.)
The feature of the changes in the peripheral nerves towhich we wish to draw attention is the considerabledestruction of the sensory terminals of muscle spindlesand tendon organs, and the relatively minor changesapparent in motor endings.These observations are based upon examination of muscles
of the foot and leg by intravital methylene-blue, by silverimpregnation of axons, by staining of myelin and nerve ter-minals with sudan-black B, and by the cholinesterase methods.The sudan technique is particularly well suited for this purpose,since it reveals with little technical difficulty degeneratingnerve fibres, and clearly shows the annulospiral sensory endingsof normal muscle spindles (fig. 1), the club endings of Golgitendon organs, and the terminal fibre in the core of paciniancorpuscles. It also shows the myelinated motor fibres runningto end-plates. Sampling interosseus and flexor digitorumbrevis of the foot 20-30 days after injection showed total lossof annulospiral endings (fig. 2) in all muscle spindles, loss ofmore than half of nerve fibres running to Golgi tendon organs,and destruction of fibres entering pacinian corpuscles. Bycontrast, the intramuscular bundles of nerve fibres running tomotor terminals showed degenerative changes in less than 5%of fibres. There were, however, many motor endings withminor but significant degenerative changes that were shownonly with the methylene-blue technique. In tibialis anteriorboth damaged and normal spindles were found, and normalspindles were also present in gastrocnemius and soleus muscles.The proportion of damaged Golgi tendon organs was alsoreduced and very few degenerating motor fibres or terminalswere found in these muscles.
In the hen distal degeneration of fibres in nerves wasfound to be greater than proximal degeneration. This
Fig. 3-Histogram showing distribution of fibre diameters in thedeep branch of the common peroneal nerve. Left, normal; right,T.O.C.P. 45 days after injection
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8. Fernand, V. S. V., Young, J. Z. Proc. roy. Soc. B. 1951, 139, 38.9. Parnitzke, K. H. Psychiat. Neurol, med. Psychol. (Lpz.), 1952, 4, 86.
finding agreed with the distribution of functional changesseen in man and with our present observations on cats.Moreover, since sensory nerves appear to be more affectedthan motor, it is deduced that fibres of large diameter areselectively damaged, and this is in fact confirmed by fibrediameter measurements. For this purpose the externaldiameters of myelinated fibres were measured in themanner of Fernand and Young 8 in the deep branch ofthe common peroneal nerve. In animals in which enoughtime was given for degeneration (i.e., 30-40 days) thenormal bimodal histogram was converted to a unimodalone, through severe reduction in numbers of fibres over10. in diameter (fig. 3). No abnormality of dorsal-rootganglion or anterior-horn cells was visible at this time,and the process must be considered as a peripheralwithering or dying-back of the affected axons.These results suggest the following points when con-
sidering physiotherapy. Since the nerve-cells and Schwanncells are intact, regeneration and remyelination of
peripheral nerve-fibres may be expected, and it is thefunctional performance of the reinnervated sensory nerve-endings upon which good recovery will depend. Thismust be especially true in mildly affected cases where themotor terminal changes will probably be relatively slight.In more severe cases, on the other hand, the ultimatefunctional recovery is likely to depend largely upon theamount of spinal-tract damage, which, as was found in theHamburg outbreak,9 may not be clinically revealed forseveral months-by which time, presumably, peripheralnerves have extensively regenerated.
V. MacD. receives a full-time grant from the Medical ResearchCouncil.
J. B. CAVANAGHM.B. Lond., M.R.C.P.
Research Fellow in Neuropathology
Department of Pathology,Guy’s HospitalMedical School,London, S.E.1
VIOLET MACDERMOTM.R.C.S.
Research Assistant
Department of Neurology,St. Thomas’ Hospital,
London, S.E.1
Reviews of Books
The Nomenclature of Disease8th ed. Drawn up by a Joint Committee appointed by theRoyal College of Physicians of London. London: H.M.
Stationery Office. 1960. Pp. 398. 22s. 6d.
IT was said that a former Principal of the first college in thefirst university in the Kingdom could detect every misprint inBradshaw within twenty minutes of receiving his monthlycopy. Reviewing this invaluable old friend presents a problemof the same magnitude. The best test of its value is to rememberthe most bizarre postmortem you ever saw: if used intelligentlythis book will give a lucid and rational name to the cause ofdeath.
There are inevitably a few omissions and errors. In the" etiological classification
"
(the spelling is regrettable anywhereand damnable in Pall Mall) fifth disease appears but salmonel-losis does not.
"
Dysentery, malarial " merely describes a
symptom of malaria. The list of bacterial parasites is arbitraryand founded on an outdated conception of pathogenic andsaprophytic organisms. The list of worms, on the other hand,is so complete that it contains many which are almost certainlyharmless to man. Ascaris lumbricoides is defined as " an
important cause of ascariasis in man ". Would the committeecare to name some other causes ? There is a long list of theintermediate hosts of Dracunculus medinensis but none fotSchistosoma spp.
1. Dutton, J. E., Todd, J. L. Brit. med. J. 1905, ii, 1259.
The catalogue of eponyms is useful and interesting. We areglad to see that Witts’ anaemia survives, but does no-one everrefer to Koch’s disease ? There may be a place called Jakein Georgia, U.S.A., but jake poisoning is probably a portman-teau form of jamake (jamaica) whence comes the ginger thealcoholic extract of which causes the trouble. Farmers’ lungand caisson disease are omitted from the list of ailments namedfrom occupation. Dhobi is mis-spelt. The Hunterian chancreowes its name to the exact definition made by the greatman and not to the fact that he poxed himself. Dutton too islisted among the victims who gave their names to diseases fromwhich they suffered. He may have caught relapsing fever, buthe and Todd were certainly the first to show that the Africandisease is transmitted by Ornithodoros moubata.1
These comments are not intended to detract one tittle fromthe reputation of a book which must remain a cornerstone ofrational medicine. We are very grateful to the committeefor their labours.
Surgery is Destined to the Practice of MedicineSir REGINALD WATSON-JONES, B.SC., M.CH.ORTH., F.R.C.S.,F.R.A.C.s.(Hon.), F.R.C.S.E.(Hon.), F.A.c.s.(Hon.), orthopaedicsurgeon-extra to Her Majesty the Queen. Edinburgh: E. & S.Livingstone. 1961. Pp. 81. 21s.
WHEN the Hunterian Orator for 1959 declared himself " a
surgeon destined to the practice of medicine " he was echoingthe sentiments of John Hunter, who held operations to be"a a reflection on the Healing Art" and "a a tacit acknowledg-ment of the insufficiency of surgery ". Sir Reginald shows howfar orthopxdics has progressed towards making redundantalmost all operative procedures. The case-records of AgnesHunt, with which his account is illustrated, contain manyphotographs of extreme deformities, large tuberculousabscesses, and draining sinuses, all due to diseases which arenow amenable to medical treatment. The text of this addresswell repays reading because it describes vividly an era in
orthopxdic surgery that is happily now over.
The Use of Isotopes in HaematologyL. G. LAJTHA, M.D., D.PHIL., member of the external staff,Medical Research Council, radiobiology laboratory, departmentof radiotherapy, Churchill Hospital, Oxford. Oxford: BlackwellScientific Publications. 1961. Pp. 83. 21s.
THIS monograph gives detailed descriptions of some of thetechniques involving radioactive isotopes that are useful forinvestigation and diagnosis in hsematology. Dr. Lajtha assumesthat his readers know all about the instruments used in isotopelaboratories and about the general techniques of isotope work.The subjects he deals with are blood-volume determinations,techniques using labelled erythrocytes, white cells, and
platelets, studies of iron metabolism, and studies of vitamin-B12metabolism. There is a final short chapter on autoradiography.The practical indications for each technique are brieflydiscussed. Selected references are provided with each chapter.None of the methods described will be new to anyone engagedin this work, but the book draws together a lot of helpfulinformation. For those thinking of applying these methods,it is a useful short account of what can be attempted at
present.
Cardiac Problems (Papers read at three symposia. TheChest and Heart Association. London: Chest and HeartAssociation. 1961. Pp. 144. 18s. 6d.).-This volume contains17 short talks given at symposia arranged by the Chest andHeart Association in 1957, 1959, and 1960. Some are in casualcolloquial vein, but others are more serious and show evidenceof careful preparation. Many aspects of cardiac disease and thetreatment of heart-failure are discussed, usually rather briefly,and the first sentence of the book-" My problem is to deal withthe differential diagnosis of cardiac and respiratory disease inabout fifteen minutes "-makes one wonder why expertsattempt the impossible.