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fibrous gliosis. Muscle biopsy (including vital staining withmethylene-blue and histological demonstration of acetylcholinesterase) was useful in demonstrating the involvementof the lower motor neurone. This investigation had theadvantage over cutaneous-nerve biopsy that it demonstratedthe changes in the nerve-endings as well as in the nerve-fibres. The changes closely resembled those seen in casesof the Guillain-Barré syndrome, and might have relative

diagnostic value-e.g., in their distinction from the appear-ances seen in diabetic neuropathy.

Abnormalities of Keto-acid Metabolism

Prof. R. H. S. THOMPSON referred to the early work inSir Rudolph Peters’s laboratory at Oxford on the changes inpyruvate metabolism in thiamine-deficient pigeons. Muchof that early work has been done with relatively unspecificmethods, such as the determination of the level of bisulphite-binding substances in the blood, and later the 2 : 4-dini-

trophenylhydrazone method. These relatively primitivemethods did, however, serve to reveal the increased levelof pyruvate in the blood in thiamine deficiency. By usinga " loading " dose of glucose to increase the sensitivity of thetest, it had been shown that many patients with polyneuritisof different types showed high blood-levels of oc-keto-acids.In only a proportion of these, however, were these high levelsrestored to normal by parenteral thiamine. To go furtherwith this problem, therefore, it was necessary to use a morespecific method to determine whether the accumulatingketo-acid was in fact pyruvic acid. In 1949, Cavallini,Frontali, and Toschi introduced the next important stepby using paper chromatography for the separation of the2:4-dinitrophenylhydrazones of different keto-acids, andmethods were soon devised for the quantitative elution andestimation of these separated derivatives. Interest had

lately been taken in pyruvate metabolism in diabetes mellitus.Since in this condition the questions of insulin sensitivityand the availability of glucose for conversion into pyruvatewere also concerned, the interpretation of blood-pyruvatelevels was particularly difficult. Also, the possibility of anaccompanying ketonaemia emphasised the need for highlyspecific analytical methods.Dr. B. McARDLE described a method for the quantitative

determination of pyruvic and cx.-ketoglutaric acids employingthe paper chromatographic separation of their 2 : 4-dinitro-

phenylhydrazones. The oc-ketoglutarate excretion in womenvaried during the menstrual cycle in much the same wayas that of citrate, being highest about the time of ovulationand during the second half of the cycle and falling immediatelybefore or with the onset of the period. The excretion of

pyruvate, related to that of creatinine, was unaffected by ageand sex ; it was often increased in hepatic and renal failureand in certain endocrine disorders. In neurological diseases,in which the excretion of cx-ketoglutarate was little affected,the pyruvate was found increased in about half the casesof polyneuritis, in muscular disorders, in subacute combineddegeneration, and occasionally in disseminated sclerosis andmotor-neurone disease.

Sweat in Fibrocystic Disease of the Pancreas

Dr. P. T. FLUTE, Dr. B. W. WEBB, and Mr. M. J. H. SMITH,PH.D., reported that the sweat of 99% of children with fibro-cystic disease of the pancreas showed persistently raised levelsof sodium and chloride. Under controlled conditions ofsweat collection, similar values were found only in primaryrenal or adrenal disorders.

Using a simple method of sweat collection, analysis ofsweat from 12 patients with fibrocystic disease gave levels ofsodium of 72 to 157 m.eq. per litre of sweat, and of chloride of68 to 145 m.eq. per litre. Sweat from 20 children with variousother diseases, and with no signs or symptoms referable tothe gastro-intestinal tract, showed levels of sodium of 4 to52 m.eq. per litre, and of chloride 9 to 40 m.eq. per litre.Thus, using the method described, amounts of either sodiumor chloride greater than 70 m.eq. per litre, in the presence ofthe typical clinical symptoms and signs, strongly supportedthe diagnosis of fibrocystic disease.

Transaminase in Coronary Thrombosis

Dr. D. N. BARON, Miss JOYCE BELL, PH.D., and Dr. CELIAOAKLEY had estimated glutamic-oxalacetic transaminasem serum by the technique of Karmen ; the normal range at

20°C was 7-25 units. In a normal individual the serum-transaminase did not vary from day to day and was unaffectedby food, normal activity, and venous constriction. Therewas no alteration in the level when serum was kept for oneweek at room-temperature or for at least two weeks frozen.A rise was found in 21 clinical cases of infarction proven byE.C.G. or necropsy findings, and in 1 clinically probablecase ; there were no false negatives. The extent and durationof the rise depend .on the size of the infarct, but usuallyexceed 75 units ; the highest level in this series was 570units. No rise was found in pulmonary embolism (7 cases)or acute abdomen (perforated peptic ulcer, biliary colic,cholecystitis, appendicitis, and intestinal obstruction),except in a patient with acute pancreatitis, in whom therewas a rise to 600 units in the first 24 hours from the onset.A value above 1000 units was found in acute hepatic necrosis,high values in infective hepatitis and active alcoholic cirrhosis,and a normal value in chlorpromazine jaundice. High valueshad been found in patients with ruptured kidney and withhemiplegia due to cerebral embolism.

MANCHESTER MEDICAL SOCIETY

AT the society’s meeting on Oct. 9 Dr. JOHN F.WILKINSON was installed as the new president, anddelivered an address entitled What’s Bred in theBone....

He reviewed a series of 2211 patients with perniciousanaemia whom he and his staff had investigated over aperiod of twenty-eight years. Comparing the treatmentof patients before liver therapy with those treated withvarious preparations of liver, stomach, folic acid, andvitamin B12 (cyanocobalamin), he demonstrated theexcellent long-term results of treatment. The duration-of life after diagnosis in the" pre-liver" days was onaverage six months : since then the outlook had changedcompletely. Now the normal expectation of life for

properly treated patients with pernicious anaemia hadbeen better even than that expected in their contem-poraries not suffering from pernicious anaemia. In Dr.Wilkinson’s series the mortality-rate was only 0-83% peryear-almost entirely from diseases other than perniciousanaemia or subacute combined degeneration of the cord.Of the 1550 patients still attending the clinic, 758 wereover 70, 283 over 80, 39 over 90, and 1 over 100.114 were still well after at least twenty-five years, 472after twenty years, and 750 after fifteen years-nonehaving developed subacute combined degeneration ofthe cord.

Dr. Wilkinson discussed the significance of familialachlorhydria or achylia gastrica in non-anæmic familiesand also in pernicious anaemia and hypochromic anæmia,as well as its association with other conditions. He gaveparticular attention to the frequency of gastric cancer(39 cases, 1-93%) in his series of patients with perniciousanaemia. He described the occurrence, distribution, andsignificance of the stomach anti-pernicious anaemia factor(h2emopoietin), the liver principle, folic acid, and

vitamin-B12 in various conditions in man and in animals,reptiles, and fishes.

Turning to the hypochromic achlorhydric anaemias inman and animals, Dr. Wilkinson demonstrated thefamilial aspects, especially of achylia or achlorhydria ;and he discussed the modes of onset by reference tothe curious effects that had been noted in circus artistesand in a series of investigations on ballet-dancers. Dr.Wilkinson also described the new National HaemophiliaScheme, its objects, and its great value in helping andsupervising the care and needs of the hæmophiliac. Inhis series of 180 patients with haemophilia, only 67%had familial histories of the disease, the remainder beingapparently due to new mutations. The importance ofmutations was illustrated by a large family of hæmo-

philiaes who had given rise to widespread and graverepercussions.