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HAROLD WARD DUDLEY, F.R.S.
839
EARLY DIAGNOSIS OF AORTIC SYPHILIS
HAROLD WARD DUDLEY, F.R.S.
THE death on Oct. 3rd of Mr. H. W. Dudley, Ph.D., F.R.S., at the early age of 47, removes one of the outstanding research workers in biochemistry as applied to medical problems. As a student at Leeds he came under the influence of J. B. Cohen, one of the first organic chemists in this country to see the promising future that lay before biochemistry. A research scholarship enabled him to spend two years in Berlin working at the structure of purines under Wilhelm Traube in Emil Fischer’s laboratory ; from there he went to Herter’s laboratory in New York where he met H. D. Dakin, another of Cohen’s old students, and entered into a fruitful collaboration with him. Most noteworthy perhaps was the discovery of the enzyme glyoxalase, which rapidly converts methyl glyoxal at body temperature to lactic acid. During the late war he was attached to the R.A.M. College in London, and was sent to the United States in charge of an anti-gas mission. On his return to England he joined the staff of the Medical Research Council as chief biochemist, a post that brought him into close contact with colleagues working in many different fields of medical research, to whom he gave freely of his deep knowledge of chemistry and his skill in complex analysis. The first problem presented to him was that of the chemical nature of the constituents of the posterior lobe of the pituitary body ; he was able to show that the pressor constituent and the constituent responsible for causing contraction of uterine muscle were separable by chemical means. He then turned his attention to the newly discovered insulin, and was the first to devise a method of preparation (still used in its manufacture) which gave a dry stable product having ten times the activity of the original crude material, and to suggest that the hormone itself was a complex protein derivative-a conclusion amply confirmed later by other workers. Meanwhile in collaboration with 0. Rosenheim and W. W. Starling he proved the constitution of spermine and spermidine, two bases now known to be general tissue constituents for which no physiological function The importance of cercan yet be even suggested. tain vasodilator constituents of the animal body with a histamine-like action for the normal functioning of the capillaries had long been emphasised by Sir Henry Dale. Dudley, in collaboration with W. V. Thorpe,- was able to identify the substance having this action with histamine itself, which was isolated from several organs under conditions which
precluded putrefactive changes. Next
came a brilliant research with Dale which led to the isolation of acetylcholine from horse and ox spleen. Here
Dudley’s analytical skill was shown at its best; his method of separating this unstable substance from choline and other substances present by means of their chloroplatinates bears the stamp of genius. Dudley’s last research, which was fortunately brought to a successful conclusion before his untimely death, dealt with the active principle of ergot. It
had been assumed that the substances active towards the uterine muscle were the alkaloids ergotoxine and ergotamine, but in 1932 Chassar Moir obtained direct evidence that aqueous extracts of ergot free from these complex alkaloids were active when administered by the mouth. The active principle must therefore be different from any of those known hitherto and Dudley undertook a chemical investigation of this unknown substance in association with the direct clinical observations of Moir. The result was the isolation of a new water-soluble alkaloid,
ergometrine, which in minute doses has the characteristic activity of ergot. This discovery of ergometrine, which solves a long-standing problem of the pharmacology of ergot and its use in therapeutics, has aroused widespread interest, as is shown by the fact that it has already been confirmed, in effect, in three other laboratories where research
independently in progress. While his main interests were definitely in the laboratory Dudley did not neglect those other biochemical activities which he was called upon to perform. From 1922-24 he was secretary of the Biochemical Society, and from 1925-30 joint editor with Prof. Harden of the Biochemical Journal. He was also for many years an assistant editor of Chemical Abstractsandwasresponsible for the high level of the section of abstracts dealing with biochemistry. His great attainments were recognised in his election to the fellowship of the Royal Society in 1930. was
EARLY DIAGNOSIS OF AORTIC SYPHILIS
SYPHILIS of the aorta usually causes death within few years of its clinical recognition. Affecting most often the ascending portion of the vessel it is liable to damage the mouths of the coronary arteries and the cusps of the aortic valves. If the inflammatory process is confined to the transverse or descending part of the arch, these vital structures escape and the prognosis is much less grave. There is reason to think that the aortic wall is invaded early in the course of syphilitic infection, and that it is not until the destructive process has been at work for many years that symptoms arise and the diagnosis of aortic syphilis is made. Hence the relatively poor results of treatment. In many diseases subjective symptoms, indicating altered function, precede any detectable alteration in structure. In aortic syphilis, however, it has been suggested that a structural change may be recognised long before symptoms arise. E. P. Maynard and co-workersclaim to diagnose such cases radiographically, and they have been able to investigate 346 patients by working in cooperation with a syphilis clinic, and investigating the cardiovascular system of every patient attending it, irrespective of the stage of the disease and the symptoms complained of. All who have studied the X ray appearances of the aorta will appreciate, nevertheless, that the recognition of slight abnormality in the width of this vessel is not easy. The width varies with age and with the shape of the chest, and can be altered by other factors such as atheroma and high blood pressure. The investigators use the method of Vaquez and Bordet for measuring the vessel width, and after excluding cases with high diaphragm, scoliosis, a systolic pressure over 140 mm. Hg, or rheumatic aortic lesions, and patients with arteriosclerosis or over fifty years of age, they accept any a
measurement over 7 cm. as pathological, and one between 6 and 7 cm. also, if the ascending aorta is prominent. Of 77 patients examined within nine years of infection, 14 had aortic syphilis, but only 4 of these had symptoms referable to the lesion. The proportion with aortitis gradually increased with the period since infection, and so did the proportion of these with symptoms ; out of 17 patients examined thirty years or more after infection 15 were found to have cardiovascular syphilis. In the 145 patients who showed evidence of aortic syphilis the mean interval between infection and evidence of 1 Arch. Internal Med.,
1935, lv., 873.
EARLY DIAGNOSIS OF AORTIC SYPHILIS
HAROLD WARD DUDLEY, F.R.S.
THE death on Oct. 3rd of Mr. H. W. Dudley, Ph.D., F.R.S., at the early age of 47, removes one of the outstanding research workers in biochemistry as applied to medical problems. As a student at Leeds he came under the influence of J. B. Cohen, one of the first organic chemists in this country to see the promising future that lay before biochemistry. A research scholarship enabled him to spend two years in Berlin working at the structure of purines under Wilhelm Traube in Emil Fischer’s laboratory ; from there he went to Herter’s laboratory in New York where he met H. D. Dakin, another of Cohen’s old students, and entered into a fruitful collaboration with him. Most noteworthy perhaps was the discovery of the enzyme glyoxalase, which rapidly converts methyl glyoxal at body temperature to lactic acid. During the late war he was attached to the R.A.M. College in London, and was sent to the United States in charge of an anti-gas mission. On his return to England he joined the staff of the Medical Research Council as chief biochemist, a post that brought him into close contact with colleagues working in many different fields of medical research, to whom he gave freely of his deep knowledge of chemistry and his skill in complex analysis. The first problem presented to him was that of the chemical nature of the constituents of the posterior lobe of the pituitary body ; he was able to show that the pressor constituent and the constituent responsible for causing contraction of uterine muscle were separable by chemical means. He then turned his attention to the newly discovered insulin, and was the first to devise a method of preparation (still used in its manufacture) which gave a dry stable product having ten times the activity of the original crude material, and to suggest that the hormone itself was a complex protein derivative-a conclusion amply confirmed later by other workers. Meanwhile in collaboration with 0. Rosenheim and W. W. Starling he proved the constitution of spermine and spermidine, two bases now known to be general tissue constituents for which no physiological function The importance of cercan yet be even suggested. tain vasodilator constituents of the animal body with a histamine-like action for the normal functioning of the capillaries had long been emphasised by Sir Henry Dale. Dudley, in collaboration with W. V. Thorpe,- was able to identify the substance having this action with histamine itself, which was isolated from several organs under conditions which
precluded putrefactive changes. Next
came a brilliant research with Dale which led to the isolation of acetylcholine from horse and ox spleen. Here
Dudley’s analytical skill was shown at its best; his method of separating this unstable substance from choline and other substances present by means of their chloroplatinates bears the stamp of genius. Dudley’s last research, which was fortunately brought to a successful conclusion before his untimely death, dealt with the active principle of ergot. It
had been assumed that the substances active towards the uterine muscle were the alkaloids ergotoxine and ergotamine, but in 1932 Chassar Moir obtained direct evidence that aqueous extracts of ergot free from these complex alkaloids were active when administered by the mouth. The active principle must therefore be different from any of those known hitherto and Dudley undertook a chemical investigation of this unknown substance in association with the direct clinical observations of Moir. The result was the isolation of a new water-soluble alkaloid,
ergometrine, which in minute doses has the characteristic activity of ergot. This discovery of ergometrine, which solves a long-standing problem of the pharmacology of ergot and its use in therapeutics, has aroused widespread interest, as is shown by the fact that it has already been confirmed, in effect, in three other laboratories where research
independently in progress. While his main interests were definitely in the laboratory Dudley did not neglect those other biochemical activities which he was called upon to perform. From 1922-24 he was secretary of the Biochemical Society, and from 1925-30 joint editor with Prof. Harden of the Biochemical Journal. He was also for many years an assistant editor of Chemical Abstractsandwasresponsible for the high level of the section of abstracts dealing with biochemistry. His great attainments were recognised in his election to the fellowship of the Royal Society in 1930. was
EARLY DIAGNOSIS OF AORTIC SYPHILIS
SYPHILIS of the aorta usually causes death within few years of its clinical recognition. Affecting most often the ascending portion of the vessel it is liable to damage the mouths of the coronary arteries and the cusps of the aortic valves. If the inflammatory process is confined to the transverse or descending part of the arch, these vital structures escape and the prognosis is much less grave. There is reason to think that the aortic wall is invaded early in the course of syphilitic infection, and that it is not until the destructive process has been at work for many years that symptoms arise and the diagnosis of aortic syphilis is made. Hence the relatively poor results of treatment. In many diseases subjective symptoms, indicating altered function, precede any detectable alteration in structure. In aortic syphilis, however, it has been suggested that a structural change may be recognised long before symptoms arise. E. P. Maynard and co-workersclaim to diagnose such cases radiographically, and they have been able to investigate 346 patients by working in cooperation with a syphilis clinic, and investigating the cardiovascular system of every patient attending it, irrespective of the stage of the disease and the symptoms complained of. All who have studied the X ray appearances of the aorta will appreciate, nevertheless, that the recognition of slight abnormality in the width of this vessel is not easy. The width varies with age and with the shape of the chest, and can be altered by other factors such as atheroma and high blood pressure. The investigators use the method of Vaquez and Bordet for measuring the vessel width, and after excluding cases with high diaphragm, scoliosis, a systolic pressure over 140 mm. Hg, or rheumatic aortic lesions, and patients with arteriosclerosis or over fifty years of age, they accept any a
measurement over 7 cm. as pathological, and one between 6 and 7 cm. also, if the ascending aorta is prominent. Of 77 patients examined within nine years of infection, 14 had aortic syphilis, but only 4 of these had symptoms referable to the lesion. The proportion with aortitis gradually increased with the period since infection, and so did the proportion of these with symptoms ; out of 17 patients examined thirty years or more after infection 15 were found to have cardiovascular syphilis. In the 145 patients who showed evidence of aortic syphilis the mean interval between infection and evidence of 1 Arch. Internal Med.,
1935, lv., 873.