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thorax, and on the posterior abdominal wall. Further

deposits are found in the axillx and deep to the sub-cutaneous white adipose tissue between the shoulderblades. The blood from this latter tissue drains roundthe spinal cord before reaching the central veins.6 7

Despite its name, brown adipose tissue which is repletewith fat is yellow (the brown becomes apparent onlyafter fat depletion), and the naked eye finds it hard todistinguish it from white adipose tissue. Indeed, at

some sites the two tissues are intermingled. But histo-logically the distinction is clear, because the brownadipose cell contains many small vacuoles of fat. Aroundeach vacuole are many large mitochondria. This

arrangement whereby the units of cell oxidation lie-nextto the source of fuel is ideal for the rapid oxidation offat. Many years ago, it was observed that brown adiposetissue has a high oxygen consumption in vitro, andDAWKINS and HULL 8 mately found that the oxidativecapacity of brown adipose tissue from the newbornrabbit exceeded that of the heart muscle. Exposure ofthe animal to cold stimulated the hydrolysis of thestored triglyceride to fatty acids and glycerol. In con-trast to white adipose tissue, brown adipose tissue doesnot release the fatty acids produced by lipolysis. Themajority of the fatty acid is either re-synthesised totriglyceride or oxidised to carbon dioxide and waterwithin the cell. As BALL and JUNGAS 9 pointed out, thisprocess is highly exothermic. The net effect of the cel-lular metabolism of fatty acid is the conversion ofchemical energy to heat.

The human infant, like the newborn rabbit, respondsto cold exposure by an increase in heat production with-out shivering. AHERNE and HULL found brown adi-

pose tissue widely distributed about the body in bothpremature and full-term infants. SILVERMAN et a1.lo

reported that the skin temperature over the nape of theneck fell less than the colonic temperature during coldexposure, and they wondered whether if this could bedue to the underlying brown adipose tissue. The brownadipose tissue of babies dying of the " cold syndrome "is depleted of fat.5 When the infant is exposed to coldthere is a rise in plasma-glycerol, without a rise in freefatty acid, which indicates that oxidation of fat is takingplace in adipose tissue.ll All this evidence stronglysuggests that heat production in brown adipose tissue isan important contributor to the infant’s response to cold.Brown adipose tissue has often been reported in the

adult human, although many pathologists still call itimmature or embryronal fat, because it was originallybelieved to be a phase in the development of white adi-pose tissue. It occasionally forms a benign tumourcalled a hibernoma. At necropsy on two elderly patientswho suffered from hypothermia, AHERNE and HULL 12found the brown adipose tissue depleted of fat. It maybe that brown adipose tissue is the site of

" chemical

6. Smith, R. E., Roberts, J. C. Am. J. Physiol. 1964, 206, 143.7. Aherne, W., Hull, D. Proc. R. Soc. Med. 1964, 57, 1172.8. Dawkins, M. J. R., Hull, D. J. Physiol. 1964, 172, 216.9. Ball, E. G., Jungas, R. L. Proc. natn Acad. Sci. U.S.A. 1961, 47, 932.

10. Silverman, W. A., Zamelis, A., Sinclair, J. C., Agate, J. F. Pediatrics,Springfield, 1964, 33, 984.

11. Dawkins, M. J. R., Scopes, J. Nature, Lond. 1965, 206, 201.12. Aherne, W., Hull, D. Lancet, 1965, i, 765.

heat production", which CANNON claimed to havedemonstrated in adult man.

If brown adipose tissue produces heat during coldexposure, it could theoretically, under pathological cir-cumstances, produce a fever. There is no evidence atthe moment that it does so. But it may be relevant tonote that many viruses, including poliomyelitis, rabies,and Coxsackie, thrive in brown adipose tissue. This

may merely reflect the rich blood-supply and high oxi-dative capacity of the tissue. Nevertheless, it is interest-ing to speculate what features of fever might be explic-able by the involvement of brown adipose tissue.

Annotations

ANALGESIC NEPHROPATHY

SINCE their introduction about 1900, the minor syntheticanalgesics have been looked on as a boon by their manu-facturers, by those seeking topics for clinical research,and by patients with neurosis, who may escape theirburdens even before the drugs can exert their variedpharmacological effects. 1 The first two groups were

right, as judged by the volume of their sales and theirwork. The patients may well have been misled, however- beguiled by a subtle foe able to steer a concealed coursebetween habituation and addiction, safety and overt

toxicity, and appearing all the more white for havingcome from coal. So successful has been the camouflagethat one well-known textbook asserts that " when oneconsiders that over 9 million pounds of aspirin are con-sumed yearly in the United States ... the high incidenceof toxic reactions to salicylate is not surprising," andanother, that " considering that thousands of tons areeaten annually significant toxic effects from aspirin areuncommon ".

Increasing precision of observation brings new know-ledge, but often this is hard to relate to formerobservations. A closer study of the wood for a whilereveals only that it consists of trees. In the articlewe published last week, Prescott 2 described a valuableand precise study of renal cell excretion before and

during the administration of analgesics. By an ingeniousnew method to distinguish renal from other " white "cells in urine, he has shown that excretion of these renalcells rises sharply after aspirin and phenacetin have beentaken, and it rises a little after paracetamol and caffeineas well. The particular advantages of this study are thatit was controlled and blind, single drugs were used inaddition to mixtures, and it involved a straightforwardmethod applicable to man. Of particular value was thedemonstration that paracetamol (a metabolite of phena-cetin) exerted little effect compared with phenacetin, forall metabolites of phenacetin have been suspect to someextent.

All this is a good step forward, and adds greatly toexisting rather circumstantial evidence about " phenacetinnephropathy "; but many questions remain to beanswered about this work and its bearing upon analgesicnephropathy in general. The observations were madeover only five days, and even during this short period theincreased cell excretion fell away sharply. Is this

phenomenon, after all, only unimportant and transient,1. Hanzlik, P. J. J. Am. med. Ass. 1913, 60, 957.2. Prescott, L. F. Lancet, July 17, 1965, p. 91.