ISSN:0003-2654    

DOI:10.1039/AN95277FX013

出版商:RSC    

年代:1952

数据来源: RSC

ISSN:0003-2654    

DOI:10.1039/AN95277BX015

出版商:RSC    

年代:1952

数据来源: RSC

ISSN:0003-2654    

DOI:10.1039/AN95277FP033

出版商:RSC    

年代:1952

数据来源: RSC

ISSN:0003-2654    

DOI:10.1039/AN95277BP043

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

APRIL, 1952 THE ANALYST Vol. 77, No. 913 PROCEEDINGS OF THE SOCIETY OF PUBLIC ANALYSTS AND OTHER ANALYTICAL CHEMISTS AN Ordinary Meeting of the Society was held at 7 p.m. on Wednesday, February 6th, 1952, in the Meeting Room of the Chemical Society, Burlington House, London, W.l. The Chair was taken by the President, Dr. J. R. Nicholls, C.B.E., F.R.I.C. At the beginning of the meeting the officers and members stood in silence as a mark of respect to the memory of the late King George VI. This meeting was organised by the Microchemistry Group of the Society, and the following papers were presented and discussed : “Some Applications of the Conway Micro-Diffusion Technique,” by N. Heron, F.R.I.C. ; “The Microchemical Determination of Iron in Aluminium Alloys,” by W. R. Nall; “The Microchemical Determination of Vanadium in Steels,” by W.R. Nall; “The Separation of Carbides from Steel and their Analytical Examination,” by R. Pemberton. NEW MEMBERS Geoffrey Cyril Ashton, B.Sc. (Liv.) ; Alfred Arnold Boucher ; Thomas William Brandon, B.Sc. (Lond.), F.R.I.C. ; Robert Alexander Chalmers, BSc. (Manc.) ; John William Dent, B.Sc. (Lond.), F.R.I.C. ; Eric Dyke, A.I.M. ; William Kenneth Ellison, B.Sc. (Durham) ; Louis Fletcher, F.R.I.C. ; Lawrence Richard Flynn, A.M.C.T., A.R.I.C. ; Albert Horsley, BSc. (Lond.), F.R.I.C.; Jack Lowen, B.Sc. (N.Y.); Geoffrey William Smith; Arthur Wool- dridge, B.Sc. (Lond.); Peter John Woosnam, BSc. (Lond.), A.R.C.S. DEATH WE regret to record the death of Bertram William John Warren NORTH OF ENGLAND SECTION THE Twenty-seventh Annual General Meeting of the Section was held a t the Engineers’ Club, Albert Square, Manchester, on-Saturday, January 26th, 1952, at 2 p.m.The Chair was taken by Mr. A. A. D. Comrie. The following were elected as Officers and Members of the Committee for the forthcoming year :-Chairman-Mr. A. A. D. Comrie. Hon. Secretary and Treasurer-Mr. Arnold Lees, 87, Marshside Road, Southport, Laiics. EZected Committee Members-Messrs. A. Alcock, W. Gordon Carey, F. Dixon, J. C. Harral, N. Heron and C. R. Louden. Hon. Auditors-Messrs. C. J. House and J. R. Walmsley. The Annual General Meeting was followed by an Ordinary Meeting of the Section a t which the following paper was presented and discussed: “The Use of Laboratory Animals as Analytical Reagents,” by A.L. Bacharach. SCOTTISH SECTION THE Seventeenth Annual General Meeting of the Section was held in Glasgow on Wednesday, January 30th, 1952, a t 12.30 p.m., and the following office bearers were elected for the forth- coming year :-Chairman-Jlr. H. C. Moir. Vice-Chairman-Mr. R. S. Watson. Hon. Secretary and Treasurer-Mr. J. A. Eggleston, Boot’s Pure Drug Co., Ltd., Motherwell Street, Airdrie, Lanarkshire. Elected Committee Members-Messrs. A. R. Campbell, F. J. Elliott, M. Pyke, S. C. Sloan, J. Sword and A. C. Wilson. Hon. Auditors-Messrs. J. Andrews and J. Gray. 167 Vice-Chairman-Mr. T. W. Lovett.168 PROCEEDINGS [vol. 77 MICROCHEMISTRY GROUP THE Eighth Annual General Meeting of the Group was held in the Meeting Room of the Chemical Society, Burlington House, London, W.11, on Wednesday, February 6th, 1952, at 6.45 p.m.At the start of the meeting members present stood in silence as a mark of respect to the memory of the late King George VI. The following Officers and Committee Members were elected for the ensuing year :- Chairman-Dr. Cecil L. Wilson. Vice-Chairma%$-Dr. A. M. Ward. Hon. Secretary- Mr. Donald F. Phillips, 101, South Promenade, St. Annes-on-Sea, Lytham St. Annes, Lancs. Hon. Treasurer-Mr. Gerald Ingram. Elected Committee Members-Messrs. W. N. Aldridge, W. T. Chambers, J. G. A. Griffiths, G. F. Hodsman, G. W. C. Milner and G. H. Osborn. Hon. Auditors-Messrs. L. H. N. Cooper and H. Childs. PHYSICAL METHODS GROUP THE Seventh Annual General Meeting of the Group was held at 6 p.m. on Tuesday, November 27th, 1951, in the Meeting Room of the Chemical Society, Burlington House, London, W.l.Mr. B. S. Cooper, B.Sc., F.Inst.P., the Chairman of the Group, presided. The Group Officers and Elected Members of the Committee for the forthcoming year are as follows :-Chairman- Dr. J. Haslam. Vice-Chairman-Mr. A. A. SmaJes. Hon. Secretary and Treasurer-Mr. R. A. C. Isbell, Hilger & Watts Ltd., Hilger Division, 98, St. Pancras Way, London, N.W.l. Members of Committee-Messrs. L. Brealey, C. H. R. Gentry, J. H. Glover, R. H. Jones, G. H. Osborn and F. R. Williams. Hon. Auditors-Messrs. C. A. Bassett and D. C. Garratt (re-appointed). The Annual General Meeting was followed by the Thirty-fourth Ordinary Meeting of the Group, at which Mr. B. S. Cooper delivered an address on “Light Sources in Chemical Analysis and Testing” ; this was followed by a discussion.POLAROGRAPHIC DISC~JSSION PANEL THE Annual General Meeting of the Polarographic Discussion Panel was held at 6 p.m. on Friday, November 16th, 1951, in the rooms of the Iron and Steel Institute, 4, Grosvenor Gardens, London, S.W.l. The following Officers were elected for the forthcoming year:- Chairman-Dr. A. J. Lindsey. Hon. Secretary-Mr. G. W. C. Milner, Building 148, A.E.R.E., Harwell, Nr. Didcot, Berks. After the business meeting the following papers were presented and discussed : “The Vibrating Electrode in Polarographic Determination of Alkyl Peroxides,” by E. R. Roberts and J. S. Meek; “A Recording Polarograph for Continuous Flow Operation,” by K. C. Overton and J. A. Lewis; “An Improved Randles-Type Cath.ode-Ray Polarograph,” by G.F. Reynolds and H. M. Davis. BIOLOGICAL METHODS GROUP THE Seventh Annual General Meeting was held at 6.15 p.m. on Thursday, December 13th, 1951 , in the Anatomy Lecture Theatre, University College, Gower Street, London, W.C.l. Mr. N. T. Gridgeman was in the Chair. The following were elected as Officers and Members of the Committee for the forthcoming year :-Chairman-Dr. H. 0. J. Collier. Vice-Chairman-L. J. Harris. Hon. Secyetary- Mr. S. A. Price, Walton Oaks Experimental Station, Vitamins, Ltd. , Dorking Road, Tadworth, Surrey. EZected Committee Members-Messrs. A. L. Bacharach, C. H. Gray, N. T. Gridgeman, J. W. Lightbown, G. F. Somers and K. L. Smith. Hon. Auditors-Messrs. D. M. Freeland and J. H. Hamence. The Annual General Meeting was followed by an Ordinary Meeting at which Mr. A. L. Bacharach, in the absence of the new Chairman, took the Chair. The following papers were presented and discussed. “A Critique of in vitro Estimation of Therapeutic Index (Toxicity Index),” by S. Morris and A. Jones; “Units of Biological Activity,” by N. T. Gridgeman. Dr. Cecil L. Wilson was in the Chair.

ISSN:0003-2654    

DOI:10.1039/AN9527700167

出版商:RSC    

年代:1952

数据来源: RSC

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April, 19521 OBITUARY 169 Obituary HENRY EDWARD COX HENRY EDWARD COX died in hospital on November Zlst, 1951, as the result of a street accident. He was born in 1892 at Lowestoft, and was educated first at a preparatory school in Beccles and then at St. Paul’s School, London. At the early age of 16 he left school and obtained a post in the firm of John Bell and Croyden, where he worked for two years. In 1911 he became an assistant to John Evans in the laboratory of Allen of Sheffield, with whom he remained for six years. In 1916 he became an Associate of the Institute of Chemistry and in 1917 left Sheffield to become assistant to George Rudd Thompson in Newport. Cox was with Rudd Thompson for five years, and during this time gained the London University degree of Doctor of Philosophy, was elected a Fellow of the Institute of Chemistry and was appointed deputy Public Analyst to Rudd Thompson for the County of Monmouth.Whilst in Newport, Cox contributed several interesting notes to The Analyst and in addition worked as an abstractor for this journal. As an abstractor, Cox was in close touch with the then Editor of The Analyst, Dr. C. A. Mitchell, who was a personal friend of Otto Hehner; knowing that Hehner wished to retire and live in South Africa, Mitchell introduced Cox to him, with the result that, in 1923, the practice of Hehner and Cox was established at 11, Billiter Square, London. This practice rapidly grew, largely through the personal energy and activity of Cox, and in 1925 he was appointed Public Analyst for the Metropolitan Borough of Hampstead, an appointment that was followed shortly after by those of Public Analyst for the County of Cornwall and for the Isles of Scilly.I n 1934 he gained the D.Sc. of London University, an honour that gave him the greatest pleasure. As an analytical chemist and consultant, Cox was without equal in matters dealing with the examination of dyed materials in connection with cases of dermatitis. He had made a special study of this field of work and contributed a most valuable paper in six parts, which was published in The AnaZyst, entitled “The Chemical Examination of Furs in Relation to Dermatitis.” This paper was followed by others dealing with the chemical aspects of dermatitis, chemicals in fabrics as skin irritants, the forensic aspects of dermatitis and by one on hair dyes.The last-mentioned paper was divided into two parts, the first dealing with the chemistry and analysis of henna and the second with the functions and reactions of phenols, and was of particular interest as it was illustrated by a cind-film in colour, prepared in great detail and with infinite care by Cox himself. Cox specialised, too, in the chemical investigations arising under patent litigation and from the discharge of trade effluents into rivers with the accompanying nuisance to riparian owners and fishing associations. Besides the papers already referred to, Cox contributed others on a variety of subjects, ranging from the occurrence of arsenic on the skins of imported apples to the available tests for identifying small quantities of war gases. He contributed also to the Encyclopedia Britannica and was the author of “The Chemical Analysis of Foods,” a book that ran into four editions and is to be found in the library of practically every Public Analyst.He was also responsible for a completely re-written revision of Wynter Blyth’s “Foods-Composition and Analysis.” Cox was a man of apparently unlimited energy, both mental and physical, as was shown by the many councils on which he served so loyally. To our Society he gave devoted and willing service and at the time of his death was serving as a member of Council as well as being Chairman of the Public Analysts and Official Agricultural Analysts Committee, and it was largely owing to his untiring efforts that the status and remuneration of part-time Public Analysts was so greatly improved.It was only a month before his tragic death that complete agreement was reached between the employing Authorities’ representatives and those representing the part-time Public Analysts. Cox served for six periods as a Member of Council of the Society and for three as Vice-president. His knowledge was profound and his judgment so sound that there was hardly a committee formed in our Society to which Cox was not automatically proposed as a member. He was kindness itself &d although obviously at times overworked and tired out, he never refused to serve on any committee if he thought by such service he was helping the Society. At the time of his death he was a member of the Committee recently constituted by the Ministry of Food to examine and make recommendations in the matter of food preservatives.Besides his faithful and valuable service to our Society, Cox had been a Member of Council of the Chemical Society, the Society of Chemical Industry and the Royal Institute of170 OBITUARY [Vol. 77 Chemistry, as well as being Chairman of the Library Committee of the Chemical Society and Chairman of the Food Group of the Society of Chemical Industry. In matters of policy or procedure in the various societies Cox often held very firm opinions, but he was rarely dogmatic. Indeed, his somewhat disarming smile was a characteristic accompaniment of the exposition of views that occasionally were so much against the general feeling that it undoubtedly required courage to uphold them publicly.And he rarely seemed to lose his temper, a quality that without doubt enhanced greatly his acknowledged value as a witness in Courts of Law. Many of our members will remember Cox with. gratitude as an Examiner in Branch E for the Fellowship of the Royal Institute of Chemistry for the friendly way in which he endeavoured to put the candidate at his ease and for the sympathetic manner in which he answered questions put to him. Cox lived at Sidcup in Kent, where he was grieatly interested in the local Boys’ Club, of which he was Vice-chairman, as well as being for about twelve years People’s Warden of Christ Church, the church he regularly attended. It always gave him the greatest pleasure to arrange a cinematograph performance on his own projector for the boys of the Club and for church members as well.He took an active part in all social events in the locality and was a popular member of the local “Brains Trust” team, and nothing pleased him more than to address district meetings on scientific matters in a language that all could understand and enjoy. Cox was a member of the Savage and Chemical Clubs, having assisted greatly in the founding and early growth of the latter. Our Society and indeed all chemical societies to which he belonged have lost a trusted and devoted member, and I personally have lost som’eone I shall always be proud to remember as a real friend and counsellor. He married, in 1922, Margaret Doughty, whom he met while he was in Sheffield, and leaves, besides his widow, one son and two daughters.ERIC VOELCKER ARCHIBALD ROBERT JAMIESON ARCHIBALD ROBERT JAMIESON, a former Vice-president of the Society, died on January 26th, 1952. Jamieson entered the service of the City of Glasgow in 1926, became Chief Assistant to the Corporation Chemist in 1935 and was appointed Corporation Chemist and City Analyst in 1945. A native of Glasgow, he was educated at Renfrew High School and graduated in Science at Glasgow University in 1924. He was admitted as an Associate of the Institute of Chemistry in 1924, became a Fellow of the Institute by exarnination in Branch E in 1930, and was elected a member of the Institute of Sewage Purification in 1934. He was keenly interested in his profession, the extent of his interest being marked by the attention he gave to the affairs of its associated societies, A member of this Society since 1930, he was a founder member of the Scottish Section and was, in turn, Member of Committee, Vice-chairman (194142) and Chairman (194344).Always closely associated with the affairs of the Royal Institute of Chemistry, he was for a number of years Honorary Secretary of the Glasgow and West of Scotland Section, again being in turn Member of Committee, Chairman and District Member of Council. As the field of his professional duties included the Chemistry of Sewage Purification, he was closely identified also with this Institute from 19%, latterly as Chairman of the Scottish Section, and Member of Council. He was a member of the Society of Chemical Industry, and also of the Chemical Society. Jamieson was well-known and respected as a lecturer on technical matters, particularly in the realms of Public Health, Sewage Purification and Civil Defence. With all his attention to professional interests he yet found time for relaxation. A great lover of the open, his activities here included both walking and climbing and, with the day’s exertions over, he was ever ready to regale his fellows with quip and song. He was a member of the Rotary Club (Glasgow), and also of the Trades House (Bonnetmakers). He leaves a widow and two young children, and. his death at the early age of 53 removes from our midst a respected official, a considerate arid helpful colleague, and a most likeable personality. R. S. WATSON

ISSN:0003-2654    

DOI:10.1039/AN9527700169

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

April, 19521 THE DETERMINATION OF CAROTENE IN GREEN-LEAF MATERIAL 171 Analytical Methods Committee REPORT PREPARED BY THE CAROTENE PANEL OF THE SUB-COMMITTEE ON T’ITAMIN ESTIMATIONS The Determination of Carotene in Green-Leaf Material Part 11. Green-Leaf Materials other than Grass THE terms of reference and the constitution of this Panel are given in Part I (Analyst, 1950, 75, 568), since when Dr. F. E. Moon has resigned and his place has been taken by Miss M, Olliver. INTRODUCTION The extension to other green-leaf material of the analytical method for determining carotene in fresh grass (Part I of this Report) was thought, when that method was put forward, to be unlikely to encounter any obstacles other than sampling difficulties. It was, however, plainly desirable to investigate both its extensibility and the emergent sampling problems; this has now been done.The choice of material for trial was governed mainly by the wish to cover a wide botanical range, but partly by availability in fresh condition. As a preliminary, some tests were made with canned spinach purke, spinach being taken as a typical dicotyledon and the form presenting no sampling difficulties. SPINACH PURBE The method recommended for carotene in fresh grass has been applied successfully to spinach purke, with two minor modifications. First, maceration of a puree is superfluous; secondly, it has been found that the mixture of equal parts of acetone and light petroleum used for the extraction of carotene from fresh grass is not ideal for a spinach puree nor, by implication, for any material whose ratio of moisture to carotene is appreciably greater than the 6000 or 7000 to 1 characteristic of fresh grass.The greater the moisture, the richer in acetone should the solvent be. A mixture of acetone and light petroleum in the ratio of 4 to 1 is recommended for this particular material. Cans representative of two specially prepared batches, A and M, of purCe were assayed for carotene in eight independent laboratories, with the mean results shown in Table I. TABLE I CAROTENE CONTESTS OF TWO PREPARATIONS OF SPINACH PURBE Laboratory I I1 I11 IV V VI VII VIII Preparation A, p. p . in. 17.9 (2) 18-7 (3) 14.7 (2) 19-4 (6) 18.8 (6) 18.3 (4) 17.0 (4) 19.8 (3) Preparation M, p.p.m. 19-2 (2) 19-8 (12) 19.3 (2) 20.7 (6) 19.9 (6) 21.0 (1) 19.5 (3) 20.9 (4) NOTE-Figures in brackets give the numbers of tests contributing to the means.The mean standard deviation of one estimate in any one laboratory is 0.744p.p.m., corresponding to a coefficient of variation of about 4. If, however, calculation is based on the interaction term “laboratories x samples” in the analysis of variance, a coefficient nearer 10 is obtained. I t can be argued that the latter is the more meaningful value; it often happens in analytical work that reproducibility tests within laboratories on sets of sub-samples yield a more optimistic estimate of precision than that obtained when the same laboratories compare results on shared samples. A coefficient of 10 is not unsatisfactory for estimates of the order of 20p.p.m., and it can be seen that, with the exception of one rogue result, the present estimates are as concordant as can reasonably be expected.All laboratories, it may be noted, agreed that preparation M is slightly richer in carotene than preparation A.172 THE DETERMINATION OF CAROTENE I N GREEN-LEAF MATERIAL [Vol. 77 FRESH GREENS The fresh green-leaf materials examined, and a synopsis of the results obtained (mostly by at least two different laboratories), are given jn Table 11. TABLE I1 CAROTENE CONTENTS OF VARIOUS GREEN-LEAF MATERIALS Brussels sprouts (Brassica oleracea gemmifera) Cabbage (Brassica oleracea capitata) . . Carrot leaf (Daucus carota) . . .. .. Chive (Allium schoenoprasum) .. .. Clover leaf (Trifolium pratense) . . .. Dandelion (Taraxacum oBcinalis) . ... Leek (Allium porrum) . . .. .. .. Nettle (Urtica dioica) . . . .’ .. .. Parsley (Petroselinum hortense) . . .. Sage (Salvia oficinalis) . . .. .. .. Sugar-beet leaf (Beta vulgaris) .. .. Watercress (Nasturtium oficinalis) . . .. .. Number of Average estimates carotene content, p.p.m. 41 20 36 2 14 4 6 6 26 3 6 8 3 to 8 1 to 4 130 40 120 50 22 110 70 70 50 70 Coefficient of variation 15 50 1 5 1 1 3 5 6 - - - In nearly all respects, including sample size, these analyses were satisfactorily carried out by the method established for fresh grass. It should be noted that materials such as brassica and leek, having a high ratio of moisture to carotene (see previous section), are more efficiently extracted with solvent mixtures containing over 50 per cent. of acetone, up to 80 per cent.being recommended for the initial extractions, with progressively smaller proportions in subsequent extractions. The coefficient of variation, based on replications within laboratories, is, for most of the items in Table 11, substantially the same as that found in the analysis of fresh grass, namely, about 4, but if the carotene content is below about 40 p.p.m. the coefficient is, understandably, higher. For materials containing less than 10 p.p.rn. of carotene, such as brassica, the error of estimation is best expressed as a standard deviakion of about 1 p.p.m. The variation is also positively correlated with stalkiness, as is to be expected from the observation that stalk usually contains little or no carotene. Brussels sprouts and cabbage, because of t’heir non-uniform pigmentation, present special sampling and preparative problems.It has been found that the variation between sprouts in any nominally homogenous batch (same variety, same picking) is not very great, and four sprouts will form a reasonable sample. Two methods of sub-sampling are recom- mended, namely, (i) the cutting of thin semi-circular sectors or wedges from each sprout, followed by chopping and mixing, or (ii) the chopping and mixing of the four whole sprouts. Wedges may be similarly cut from cabbage. The importance of proper sampling of cabbage and sprouts is demonstrated by the results obtained from various leaf layers in the course of this work. Integration of these results makes possible an expression of carotene distribu- tion between three concentric shells and the heart of a typical mature cabbage or sprout, the four parts being so cut as to be of equal weight.The outer quarter was found to contain 75 per cent. of the total carotene, the next inner contained 15 per cent., the next 7 per cent. and the heart 3 per cent. (One Sells sprout, after removal of the outside damaged leaves, was found to contain about 0.2 mg of carotene, and a large Winningstad cabbage, similarly trimmed, about 5 mg of carotene.) The necessarily heavy sampling of plant material with a very small or very hetero- geneously distributed carotene content can alternatively be handled with a mechanical macerator,* but the operator must satisfy himself that full recovery (e.g., no losses of carotene by splashing) is being effected and that no chemical changes occur; this is best-although even then not certainly-secured by replacement of the air with an inert gas, such as carbon dioxide, hydrogen or oxygen-free nitrogen. * On page 569, line 20, of Part I of this report (Analyst, 1950, 75, 568-573) mechanical homogenisation was, by a misprint, described as “more efficient” instead of “no more efficient” than the hand grinding technique. The error has been corrected in the reprints.

ISSN:0003-2654    

DOI:10.1039/AN9527700171

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

April, 19521 GOODWIN : THE EVALUATION OF AMOEBICIDAL SUBSTANCES in ViVO The Evaluation of Amoebi cidal Substances in 173 vivo BY L. G. GOODWIN (Presented at the meeting of the Biological Methods Group on Saturday, October 27th, 1951) The occurrence of Entamoeba histolytica in man and other hosts is The effect of drugs on this infection in man and animals, and The interference of E. rvturis in the treatment of amoebiasis is also described. particularly of emetine, diodoquin or carbarsone on rats, is detailed. mentioned. I SHOULD like first to remind you of the nature of amoebic infection in man. Entamoeba histolytica is a curious parasite. In the majority of people who harbour it in their guts it lives quite happily, feeding upon bacteria, and produces, at the most, only minute areas of damage to the wall of the large bowel.In such conditions, the infection is usually symptom- less, the amoeba quietly completes its life history and the host passes cysts in his faeces. Occasionally, for reasons that we do not understand, but that may depend upon particular strains of the amoeba or the presence of certain bacteria, it acquires a thirst for blood and plays havoc with the gut wall. It produces deep and extensive ulceration, and blood and mucus are passed in the stools. The amoebae feed themselves with red blood cells and are swept out of the gut to their death before they can form cysts. They occasionally enter the portal vessels and are carried to the liver, where they give rise to amoebic hepatitis or liver abscess. In the design of a laboratory test for new remedies for a disease of this kind, we must be careful to choose a suitable host and a suitable strain of amoeba.Monkeys are easy to174 GOODWIN 1 THE EVALUATION OF AMOEBICIDAL [Vol. 77 infect experimentally and frequently carry natural symptomless E. histolytica. The action of drugs in this infection has been investigated by Anderson in California, who has obtained very useful information. Monkeys, however, are expensive and difficult to handle, and we need something smaller. Kittens, when inoculated per rectum with amoebae from a human patient or from cultures, suffer from very severe ulceration, leading to a bacterial septicaemia that kills them in a few days. However, the infection in kittens does not respond to treatment with emetine or with any of the other drugs known to have activity in human amoebiasis, so that we cannot really expect to discover new amoebicides with an infection of that type.Rats have been known for many years to be susceptible to infection with E. histoZytica. They can be infected experimentally by giving cysts by mouth in the natural way, although infection takes some time to develop and is not always established. A more certain way is to inoculate a culture of the amoebae directly into the caecum, exposed under anaesthesia through a small incision in the abdominal wall. This produces ulceration in all of the animals if the strain of amoeba is a suitable one and if the rats are very young. This method, with weanling rats, was first described by W. R. Jones in 1946.It was believed that the infection cured itself spontaneously in a few weeks; however, my colleague Dr. Neal has shown that with some strains of amoeba the infection persists for many months and the animals pass cysts in their faeces. Moreover, different strains of amoeba from acute, sub-acute and chronic human infections usually produce similar types of infection in the rat. Differences in the virulence of strains may be associated with differences in the accompanying bacterial flora, but this we do not yet know for certain. You will see, therefore, that the infection in the rat is closely similar to the infection in man. When infected rats are treated, for one week after inoculation, with drugs such as emetine, diodoquin or carbarsone, they show less severe lesions of the caecum than do untreated control animals.With sufficiently large doses the rats are cured, and then no amoebae can be found in their caecal contents. The severity of the lesions, or the proportion of a group of rats freed from amoebae by a dose of a drug, can be used as quantitative measures of effect and form the basis for an assay of potency. This method, then, agrees well with the conditions required for a good biological test. Untreated control animals always become infected, and emetine and other drugs have a recognisable action. The infecting organism is derived from man and produces lesions similar to those in man. A simple test upon the acute infection is completed in one week. I must, however, mention a difficulty met early in the course of our work with the infec- tion, one that I know has also given Dr.Fulton a good deal of trouble. A harmless commensal amoeba, E. muris, is often found in the caeca of rodents. With experience it is not difficult to distinguish this organism from E. histolytica under the microscope, but difficulties arise if there is a mixed infection and both species are present. E. mu& does not respond to treatment with emetine, so that its presence in an experiment of the kind described is a disaster. The infection is transmitted to young rats in foodstuffs and bedding that have been soiled by the excreta of rodents carrying the cysts of E. muris. There is a simple way of avoiding the trouble. The rats must be bred from a stock free from E. muris, and all cages, wood-wool and sawdust used for the experiment must be sterilised before use.Food stocks must be protected from contamination. Hamsters, which often carry very heavy infections, should not be kept in the same room as the rats. THE WELLCOME LABORATORIES OF TROPICAL MEDICINE 183, EUSTON ROAD LONDON, N.W. 1 (After the presentation of the above paper a film made by Dr. Goodwin to illustrate the method of carrying out the test was shown.) DISCUSSION DR. J. D. FULTON said he was still troubled with E. ? n u k in his rats, and asked if Dr. Goodwin was still able to keep his rats free from it. He said that his difficulty was limited space, and that he had to keep rats, mice, hamsters and cotton rats all in the same room; I?. rnurzs was always found in the guts of the last two species.DR. GOODWIN replied that he was still able to keep his rats free from E. muris. PROFESSOR BUTTLE enquired about the effects of antibiotics on rats.April, 19521 SUBSTANCES in vivo 176 DR. GOODWIN replied that aureomycin, streptomycin, terramycin and penicillin all had some effect DR. G. M. FINDLAY asked if it was proved that the bacterial flora was responsible for the dying-out DR. GOODWIN said that it was probable that this was so, but that nobody had proved it. DR. F. HAWKING said that in general, as soon as possible after definite activity has been found in a new chemical series in the search for new chemotherapeutic substances, a preliminary clinical trial should be arranged, as- (i) the relation between activity in the laboratory and therapeutic activity in man was not at all close. Often substances that were very active on laboratory infections had no action in man. Occasionally substances that were only mediocre in the laboratory were highly successful in man, (ii) the substance might. cause peculiar toxic effects in man, e.g., peripheral neuritis or toxic action on the finger nails, which would not be revealed by animal experiments. The results of this preliminary clinical trial were very valuable in planning the further development on rat amoebiasis, but that, as in human cases, the amoebae were not eradicated. of amoebic infections in people who had returned to Britain from the tropics. of the chemical series involved.

ISSN:0003-2654    

DOI:10.1039/AN952770173b

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

April, 19521 SUBSTANCES in vivo 176 The Evaluation of Chemotherapeutic Agents Directed Against Trypanosome Infections BY E. M. LOURIE (Presented at the meeting of the Biological Methods Group on Saturday, October 27th, 1951) Refined statistical methods have been essential for the development of techniques of biological standardisation, but in the search for new compounds of clinical value they are useless or deceptive unless appropriate experiment a1 procedures are used. In the control of sleeping sickness in Africa the tendency is for “mass- treatment” to be replaced by “mass-chemoprophylaxis.” The compounds now used for this purpose are highly effective, but are not necessarily the best that might be devised. There is accordingly need for a simple and rapid method for screening compounds as to their prophylactic activity.There is good reason to believe that the composition of certain trypano- cides of the melaminyl series, already fairly extensively used in the field, cannot be guaranteed by chemical or physical means. It is therefore necessary that standard preparations of these substances should be established and that batches intended for use in man should be biologically compared with those standards. THE history of the systematic evaluation of drugs against infective disease really begins with trypanosomiasis, because it was with trypanosome infections that Ehrlich, some fifty years ago, began his pioneer investigations of new chemotherapeutic agents. The measures of toxicity and of efficacy he used, namely the “minimal lethal dose” and the “minimal curative dose,” have since been much criticised as being either impossible to determine within reasonable limits of error, or indeed as having no meaning at all, in face of the notorious variability of biological reactions.The later introduction of the concept of the LD50 and the ED50 by Trevanl and the elaboration of methods of determining the fiducial limits t o these end-points and of the direction and variance of the dose - response curve have been of inestimable value towards clear thinking and towards the evolution of techniques of biological standardisation. Yet there is no reason to believe that Ehrlich’s search for chemo- therapeutic agents of clinical usefulness would have met with any greater success if he had striven to improve on his own crude statistical methods.LIMITATIONS OF SCREENING TESTS IN MOUSE INFECTIONS It is easy to justify the statement that a more refined statistical technique would not necessarily have led Ehrlich to select better chemotherapeutic agents than he in fact chose. In so-called screening tests in laboratory infections, the species of animal used is neither man176 LOURIE THE EVALUATION OF CHEMOTHERAPEUTIC AGENTS [Vol. 77 himself nor the large and expensive domestic animal for whose eventual benefit the tests are performed; the circumstances and the type of infection are usually so different in the laboratory animal from those in man or the domestic animal that the result in the laboratory can often at best give no more than a slight hint at the possible clinical effect. A series of drugs arranged in the order of their efficacy in mice cannot be expected to fall into the same order when arranged according to their usefulness in man.or the domestic animal. For the moment one example alone will suffice. On the basis of the chemotherapeutic index in mice, suramin would be placed far ahead of tryparsamide,2 yet .in mah tryparsamide is much the more valuable of the two. If the relative efficacy of two compounds can be so spectacularly reversed when tested first in mice and then in man, it is clearly futile merely to arrange drugs in a close order of their efficacy in mouse infections, with the aid of refined statistical procedures, where the object is limited to the selection of those that are most likely to be useful in man.In recent tests of cinnoline compounds in rnice infected with the cattle trypanosome, T . congolense, one member of this chemical series was carefully compared with antrycide methyl~ulphate.~ Where the chemotherapeutic index was defined as the LD50/CD50, antrycide was found to be slightly the more effective compound of the two, but where the index was defined as the LDlO/CD90, which approximates more closely than the LD50/CD50 to the requirements of actual clinical practice, there was no significant difference between the two compounds. A statistical exercise of this nature may serve the useful purpose of encouraging the field worker to test a compound he might otherwise reject without trial, but it does practically nothing to increase the 1ik:elihood that the trial will in fact show the drug to be of great clinical value.Let us examine more closely the limitations imposed by a dependence on infections in small laboratory animals for the initial screening tests of anti-trypanosomal drugs. One essential and obvious difficulty is that absorption, excretion and degradation of a drug may be so completely different in two species of animal that there can be no assurance that trypanosomes will be equally exposed to the drug in the laboratory animal, on the one hand, and in man (or the domestic animal), on the other. Then there are the differences between the type of infection in the laboratory animal and in the natural host. The infection usually used for screening tests in mice is of the acute fulminating septicaemic type, and in man or domestic animals it is of a chronic, or relatively chronic, tissue-invading type, in which contamination of the circulating blood is relatively slight and easily controlled. The problem is to reach the trypanosome in the more or less inaccessible spaces to which it retreats and in which at least some species of trypanosome may perhaps assume an increased degree of resistance even if the drug were capable of reaching it there.PRELIMINARY INVESTIGATIONS OF POTENTIAL TRYPANOCIDES I N LABORATORY ANIMALS OTHER ’THAN MICE The work that led to the introduction of tryparsamide for human trypanosomiasis by American workers4s5 in 1919 took full account of the fact that tests in the septicaemic infection of mice cannot be a reliable guide to the results that might be obtained in the type of infection that occurs in man.For this reason much reliance was placed on trials in rabbits rather than in mice, since trypanosome infections in rabbits are normally of a chronic, tissue- invading type and, to that extent, approximate more nearly than the septicaemic infections of mice to the type that occurs in man. However, the mere device of testing the drugs in rabbit infections is not enough. Pentamidine was found to be more effective than tryparsamide in rabbits,6 yet it proved to be far inferior to tryparsamide in the late stage of human trypanosomia~is.~~~ It is for this stage, characterised by involvement of the brain and cerebrospinal fluid, that the need for new drugs is greatest. A measure is therefore needed of the drug’s efficacy in dealing with trypanosomes in tissue spaces other than those invaded in the rabbit, namely, in the brain and cerebrospinal fluid.Tests of new drugs for human trypanosomiasis should accordingly include attempts a t determining their power of penetrating the blood - brain barrier or of entering the cerebrospinal fluid. These two properties are not necessarily synonymou~,~ but simple routine methods of measuring the power of penetrating the blood - brain barrier are not available for many types of drug, and there are good reasons for accepting a drug’s powers of entering the cerebrospinal fluid in trypanocidal form as some indication of its potential usefulness in late human trypano- somiasis.lo’ll Such tests can easily be made in rabbits, and there is at least some suggestionApril, 19521 DIRECTED AGAINST TRYPANOSOME INFECTIONS 177 of their potential value in the facts that Rollo, Williamson and Lourie12 found that Friedheim’s melaminyl arsenical, melarsen, entered the cerebrospinal fluid in trypanocidal form to much greater effect than any other compound tested, and that the latest report from Nigeria13 has shown this drug to be at least as effective as tryparsamide in advanced T.gambiense infections in man. In trypanosomiasis of cattle, unlike human trypanosomiasis, the main problem is not invasion of the central nervous system with consequent failure of the drug to reach the trypanosome in that particular site. The trypanosome (T. congolense) may, however, remain hidden for long periods of time in some unknown site, and Fiennes14 believes that such cryptic infections do much damage and constitute one of the main difficulties in the chemotherapy of trypanosomiasis in cattle.He has produced evidence that cardiac muscle may be one of the sites of such cryptic infections. Here also, therefore, tests on the septicaemic infection of mice cannot afford any precise forecast of eventualities in the host for which the drug is finally intended. THE SPECIES OR STRAIN OF TRYPANOSOME USED IN SCREENING TESTS Complications in interpreting the results of mouse screening tests in terms of the infection in man or domestic animals arise not only because of differences between the species of host and between their reactions to the parasite, but also because the species or strain of parasite used in the mouse may be very different from those of natural infections in man or domestic animals.When a strain of T. rhodesiense was used for screening tests in mouse infections during the work which led to the use of pentamidine,6 some of the more important charac- teristics of the strain were very different from those it had exhibited when it was originally isolated from man many years earlier; the anomalous situation arose where a group of drugs, the diamidines, was introduced into clinical practice for the treatment of T. gambiense infections although it has found little or no place in the treatment of natural infections by the very species, T. Yhodesiense, against which it was originally screened.15 In screening tests of drugs intended for the treqtment of cattle trypanosomiasis, one difficulty is that, although the most important species in cattle, T.congolense, is inoculable into mice, another dangerous and widely-prevalent pathogen, T. vivax, cannot be readily maintained in small laboratory animals and so cannot be used for simple and rapid screening tests. CHEMOPROPHYLACTIC ACTIVITY The laboratory investigation of new drugs intended for trypanosomiasis must take special account not only of the pathology and parasitology of natural infections, but also of the actual practice of trypanosomiasis control in the field. This is at present undergoing a revolutionary change. For more than 40 years an important feature in campaigns against sleeping sickness has been the practice known as “mass-treatment ,” involving examination of all the inhabitants of a large area and the administration of a full course of curative treatment to all who are found to be infected, whether as invalids or carriers.Few are aware of the prodigious scale on which such work has been carried out by the branches of the medical services dealing with sleeping sickness in tropical Africa. Every year, for many years, millions of people have been examined in the course of this work,16 treatment being given where necessary. The tendency now is for “mass-treatment” to be replaced in many territories, especially French and Belgian, by “mass-prophylaxis,” which involves the administration of a drug with prophylactic activity to every uninfected person in the selected area; pentamidine has become very widely used for this p u r p o ~ e .~ ~ ~ ~ ~ ~ ~ ~ p20 Valuable though pentarnidine is as a prophylactic agent, it is not necessarily the best that might be devised, and there is, accordingly, need for a simple rapid technique in screening compounds for their prophylactic activity. The ordinary tests for therapeutic properties are useless for this special purpose. For example, the polymer of Friedheim’s antimonial analogue of melarsen, known as MSb, far outstrips pentamidine as a prophylactic agent in mouse infections, while the monomer is practically devoid of prophylactic action.21 Y l 2 Yet the difference between the polymer and the monomer in therapeutic activity is relatively slight,21 so that the ordinary tests of therapeutic activity would fail completely to reveal the particular difference between these two preparations that is of greatest significance to the worker in the field.The kind of screening test for prophylactic activity that might perhaps serve as a routine in mice would involve the inoculation of a standard number of trypanosomes at a fixed time (say178 LOURIE : THE EVALUATION OF CHEMOTHERAPEUTIC AGENTS [Vol. 77 2 weeks) after administering the drug, and examining the blood after a further fixed period (say a further 2 weeks). BIOLOGICAL STANDARDISATION OF COMPOUNDS DIRECTED AGAINST TRYPANOSOMIASIS I have so far discussed drug assay only from the point of view of discovering new chemotherapeutic agents. The other, and entirely different, purpose for which drugs are assayed against laboratory infections is to confirm the freedom from undue toxicity and the potency of individual batches of established chemotherapeutic agents whose constitution cannot be guaranteed by chemical or physical means.Members of the arsphenamine group and suramin come into the category of substances for which such biological standardisation is still regarded as necessary. The methods used for this purpose need not be described here, for they have recently been well summarised by Goodwin.22 It was the alarming and unpredictable incidence of severe toxic reactions or of therapeutic inefficacy (against syphilis) , in a type of compound that could not be produced to a uniform physico-chemical pattern , that led to international agreements in 1925 on biological standards for the arsphenamines, and on methods of compairing batches intended for clinical use with the agreed standards.The time seems to have anived, if indeed it is not already overdue, for biological standards to be provided for some of the newer trypanocides, which also surely come into the category of substances that cannot be accurately characterised by chemical or physical means. These are the compounds elf Friedheim’s melaminyl series, especially “Me1 B,” which is a condensation product of melarsen and BAL (used for therapy) and MSb, mentioned above (used for prophylaxis). Me1 B, in particular, has already been fairly extensively tested in man, even before the publication of any results of tests on laboratory infections. The clinical reports on this substance have almost inevitably been highly con- flicting, both as to toxicity and to efficacy.13s23,24J5s26 I t is certain that some of the batches used in man have been extremely toxic.MSb has also been tested as a prophylactic agent under field conditions, in trials involving at least seven hundred subjects, with inconclusive but encouraging results.27 In order that a proper judgment should at last be formed of these melaminyl substances, and in the interests of the patients themselves, it is necessary that agreed standard prepara- tions should now be established and that batches intended for use in man should satisfy the requirements of biological tests, of which the details remain to be decided in the light of a careful study of the standard preparations.From the chemical nature of melarsen it is likely that reliable methods of preparation and chemical characterisation will soon render a biological standard and biological tests unnecessary for this particular member of the group, but for Me1 B and MSb standards will probably continue to be necessary for a much longer time. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. REFERENCES Trevan, J. W., PYOC. Roy. SOL, B, 1927, 101, 433. Yorke, W., Murgatroyd, F., and Hawking, F., Ann. Trop. Med. Parasitol., 1931, 25, 313. Lourie, E. M., Morley, J. S., Simpson, J. C. E., and Walker, J. M., Brit. J . Pharmacol., 1951, Jacobs, W. A,, and Heidelberger, M., J . Exp. &‘led., 1919, 30, 411. Brown, W. H., and Pearce, L., J . Amer. Med. Ass., 1924, 82, 5.Lourie, E. M., and Yorke, W., Ann. Trop. Med. Parasitol., 1939, 33, 289. Saunders, G. F. T., Ibid., 1941, 35, 169. Lourie, E. M., Ibid., 1942, 36, 113. -, Trans. Faraday SOC., 1943, 39, 340. Voegtlin, C., Smith, M. I., Dyer, H., and Thompson, J. W., Publ. HltJz. Rep. Wash., 1923, 38, 1003. Hawking, F., Hennelley, T. J., and Quastel, J . H., J . Pharmacol., 1937, 59, 157. Rollo, I. M., Williamson, J., and Lourie, E. ILL, Ann. Trop. Med. Parasitol., 1949, 43, 194. Duggan, A. J., and Hutchinson, M. P., Trans. I?. SOC. Trop. Med. Hyg., 1951, 44, 535. Fiennes, R. N. T.-W.-, Ibid., 1951, 44, 605. Lourie, E. M., Comment on Proceedings of a Mulago Staff Clinical Meeting, Trop. Dis. Bull., Wilcocks, C., Corson, J. F., and Sheppard, R. L., “A Survey of Recent Work on Trypanosomiasis Harding, R. D., and Hutchinson, M. P., Trans. A?. SOC. Trop. Med. Hyg., 1950, 43, 503. Scaillet, L., and Haddad, E., Ann. SOC. Belge Me’d. Trop., 1950, 30, 1525. Jonchbre, H., Bull. SOC. Path. Exot., 1951, 44, 83. Kernevez, H., and Chassain, J., Ibid., 1951, 44, 337. 6, 643. 1950, 47, 526. and Tsetse Flies,” Bureau Hyg. Trop. Dis. Review Monograph No. 1, London, 1946.April, 19521 DIRECTED AGAINST TRYPANOSOME INFECTIONS 179 Friedheim, E. A. H., Vogel, H. J., and Berman, R. L., J . Amer. Cham. SOL, 1947, 69, 560. Burn, J. H., Finney, D. J., and Goodwin, L. G., “Biological Standardisation,” Second Edition, Friedheim, E. A. H., Amer. J . Trop. Med., 1949, 29,. 173. Le Rouzic, Bull. Me’d. de Z’Afrique Occident. Frang., 1949, No. SpBc., 63; Trop. Dis. Bull., 1950, Commission du Me1 B, Ibid., 1949, No. Spkc., 73; Trop. Dis. Bulb., 1950, 47, 449. Ceccaldi, J., Trinquier, E., Arnoult, H., and Menu, P., Bull. Soc. Path. Exot., 1950, 43, 83. Le Rouzic, Bull. Mbd. de l’dfrique Occident. FranF., 1949, No. SpBc., 53; Trop. Dis. Bull., 1950, 21. 22. 23. 24. 25. 26. 27. Oxford University Press, 1950, Chapter XXII. 47, 449. 47, 451. DEPARTMENT OF PHARMACOLOGY UNIVERSITY OF OXFORD

ISSN:0003-2654    

DOI:10.1039/AN9527700175

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

April, 19521 DIRECTED AGAINST TRYPANOSOME INFECTIONS 179 Rapid X-Ray Quantitative Analysis of Crystalline Powders With Particular Reference to Titanium Dioxide Pigments BY W. HUGHES AND H. SMITH (Presented at the meeting of the Physical Methods Group on Friday, October 19th, 1951) A simple X-ray diffraction camera is described, the action of which is based on the flat powder layer method. The camera can be constructed easily and it gives a tenfold reduction in exposure times compared with a normal 9-cm powder camera. Specimen preparation is simplified, and where large numbers of specimens are involved there is considerable saving of time in processing the film. The instrument has proved useful for very rapid qualitative and quantitative examinations of crystalline powders. The accuracy with rutile - anatase mixtures is about &2-6 per cent.A second method of quantitative analysis by means of a Geiger-counter X-ray spectrometer is described. No photographic processing is required and the accuracy with rutile - anatase mixtures is probably better than f 1 per cent. THE method of analysis of crystalline powder mixtures by X-ray diffraction techniques has been used for many years and is adequately described in the literature. Briefly, a powder mixture irradiated by X-rays gives a composite diffraction pattern, consisting of the super- imposed unique patterns of the individual components. A comparison of the intensity of suitably chosen lines in the constituent patterns gives an estimate of the amounts of the various substances present in the mixture.The comparison can be made visually or photo- metrically from a photographed record of the pattern as in the first method described below, or by direct intensity measuring devices such as the ionisation chamber or Geiger-counter tube, as described in the second method. X-ray diffraction methods are not generally regarded as particularly sensitive for detecting small quantities of materials, nor is indiscriminate application possible ; but by ingenious adaptation or careful development, the methods can be applied to many analyses to give a high degree of accuracy. Rooksbyl for example, showed that 0-1 per cent. of calcium oxide in magnesium oxide and 0.2 per cent. of zinc oxide in zinc sulphide could be detected. The following methods were developed specifically for the rapid analysis of mixtures of the anatase and rutile forms of titanium dioxide pigments.They may be of more general interest however, as they should be adaptable to the analysis or examination of other powder mixtures . METHOD THE FLAT POWDER LAYER CAMERA METHOD- In general, in the past, the analysis of crystalline powders by X-ray diffraction techniques has involved the use of Debye-Scherrer cameras, which require that the specimen be in the form of an accurately centred thin cylinder. The major defects of the Debye-Scherrer180 HUGHES AND SMITH : RAPID X-RAY QUANTITATIVE [Vol. 77 camera compared with those of the flat powder layer camera, are the relatively long exposures and the necessity for standardisation of specimen preparation.The need for a method that involved considerably reduced exposure times and a simplified technique of specimen preparation arose when many hundreds of anatase - rutile mixtures were to be analysed in such a short period of time that conventional methods were out of the question. This need was met admirably by adopting the flat powder layer method developed by Brentano.2 The principle is illustrated in Fig. 1, in which A represents the Fig. 1. The principle of the flat powder layer camera method distance of the X-ray source from the point of intersection of the incident beam with the powder layer, and B, the distance of the point of observation from the same incidence point. The glancing angle of incidence is a and the glancing angle of reflection is p.The Bragg angle is 8, where a + 18 = 28. The powder layer is sufficiently thick to absorb fully the incident radiation and is normal to the plane containing the incident and reflected beams. sin o! A the reflected beam is partially focused round the point of observation and that when this focusing condition is satisfied the absorption by the specimen is proportional to p(1 + A/B), i.e., it is independent of 8, where p is the linear absorption coefficient of the powder. The advantages of this method are, (a) the reduced exposure times which follow from the para- focusing property of the flat specimen, (b) rapid preparation from the simple nature of the specimen, and (c) the elimination of the necessity for special care in specimen preparation because the absorption is independent of 8.The flat powder layer camera as developed b:y Brentano is not of particularly simple construction and in this respect suffers in comparison with the conventional Debye-Scherrer camera. However, during routine examination of powder mixtures of two crystalline substances only, it is possible to introduce a major simplification. Inspection of the Debye- Scherrer photographs (Fig. 2, a, b and c ) of titanium dioxide pigments shows that convenient lines for comparison lie in the angular range 8 = 17" to 8 = 34". This range contains well resolved lines of such relative intensity that small quantities of anatase are more readily detected, and it corresponds to the compositions important in the pigment industry. A flat powder layer camera was designed and constructed that would take photographs over this restricted angular range and in which maximum focusing was attained in the middle of the range.Fig. 3 is a diagram and Fig. 4 a photograph of the camera. The instrument consists essentially of a slit system and collimator, a specimen holder and its mount, and a film holder. Exposures are short by virtue of the short target-specimen- film distances, the relatively wide slit-system giving an appreciably divergent beam from a line focus tube, and because of some degree of focusing by the relative positions of beam, specimen and film. The camera, Figs. 3 and 4, is built on a flat metal plate that is fixed on a camera stand by the conventional hole, slot and plane arrangement. The source of X-rays, S, used, was the vertical line focus of a Metropolitan Vickers Raymax unit and B is a single slit 2.5 mm high and 0.8 mm wide; the distance SB is 6.5 cm.A removable Perspex specimen holder, C, whose vertical plane is set at an angle of 28" to the beam, has I t can be shown easily that when - s i n p = BFig. 2. X-ray powder photographs: ( a ) and ( f ) , rutilc; ( b ) and ( e ) , 30 per cent. o f rlltilc + 50 per cent. o f anatax,; (0 and ( d ) , anataseFig. 3. 13, single slit; C, removable Perspcx specimcn holder; I), depression; Iliagram of the flat powder layer camera. E, film-holtlrr; 1;, film; G, p-filter; H, shield; S, source of X-rays Fig. 4. The flat powdm layer cameraApril, 19521 ANALYSIS OF CRYSTALLINE POWDERS 181 a countersunk depression, D, to hold the powder centred on the area of incidence of the primary beam; distance BD is 0.5 cm.The film holder, E, is 24 inches long and is constructed from brass curtain rail to carry a strip of film 30 cm x 3 cm (the conventional strip-size in 9-cm Debye-Scherrer cameras) in a vertical plane inclined a t an angle of 45" to the incident beam. The plane of the film is then perpendicular to a reflected beam, whose Bragg angle is 22.5". A window 1 crn high and 2.5 cm long is cut in the film holder centred about this angular position. The distance, DF, of the window from the specimen is 4-0 cm. All reflected rays passing through the window will be focused to some extent as sin 28"/sin 17" t SD/DF, i.e., the focusing condition is satisfied for a beam passing through the centre of the window.The film strip is wrapped in black paper and pressed against the window by two spring-loaded rollers. Ten exposures can be made on one 30-cm strip of film by moving the film laterally after each exposure. A 15-filter, G, is placed at this point so that it can also function as an attenuator of fluorescent radiation from the specimen. A shield, H, prevents diffracted rays from the edge of the slit, from falling on the film. The specimen holder is held against the face of the support by a ball and spring (a conventional door fitting) and is fixed in position by vertical and horizontal stops. Specimen preparation is carried out simply by pressing the powder into the hollow drilled in the holder and by smoothing the powder surface flush with the face of the holder.With titanium dioxide pigments the powders are packed dry without diluent or binder, but when pastes or non-cohering powders are used, a strip of cellophane adhesive tape conveniently keeps the specimen in the holder. If the specimen cannot be sufficiently finely ground to give uniform diffraction lines in the stationary state, the specimen holder would have to be constructed so that it could rotate about a horizontal axis, perpendicular to the specimen face and passing through the centre of the powder. Fig. 2, d, e and f show that the photographs taken with this camera are as satisfactory for visual comparison or photometric measurement as full Debye-Scherrer patterns. The great reduction in exposure times is illustrated by those for the photographs in Fig.2. The full Debye-Scherrer patterns were obtained with a Unicam 9-cm camera after exposure for 30 minutes. The small photographs from the powder layer camera were obtained after exposure for 3 minutes. In practice there is a further considerable economy in time by virtue of the multiple exposures carried by the same strip of film. Under certain circum- stances the time spent in processing film can be reduced tenfold. The performance of the instrument can be assessed from the fact that from photographs of synthetic mixtures of known composition (in steps of 5 per cent.) as standards, four inde- pendent observers each estimated unknown mixtures to within 2 per cent. of the actual composition, and their results were within 2 per cent. of each other.Apart from the analysis of rutile - anatase pigments for which it was specifically designed, the camera has been found very useful for rapid qualitative examinations, particularly of nearly pure minerals. In such circumstances a rapid preliminary examination can be a valuable guide to a subsequent full chemical analysis. In addition, it has been possible to examine pigmented vitreous enamel panels and applied paint films. This type of camera could probably be applied with equal success to the analysis of any binary crystalline mixture of uniform quality, the necessary modification being made to give the preferred angular range. THE GEIGER-COUNTER X-RAY SPECTROMETER METHOD- In recent years the Geiger-tube with associated scaling circuits has been increasingly used in X-ray work for the direct measurement of intensity; the advantageous elimination of photographic processing, coupled with an increased range of linearity is likely to lead to a more widespread use of instruments that rely on this method of measurement.The instrument used for the work described here was the Norelco Geiger-counter X-ray spectrometer manufactured by North American Philips Co., and the method developed proved so simple and reliable that it has now become incorporated in factory process control. The instrument is described by Bleeksma3 and a critical examination of its performance has been carried out by Lonsdale.4 The flat powder layer method is again utilised and consequently the camera has similar advantages to those of the camera described above.It consists essentially of a source of X-rays, a slit system defining a divergent beam, a specimen holder, a second slit system mounted in front of an end-window Geiger-tube which is carried on a graduated arc centred on the specimen. The specimen rotates at half of the angular182 HUGHES AND SMITH : RAPID X-RAY QUANTITATIVE [Vol. 77 velocity of the Geiger-tube so that the para-focusing condition is satisfied for all settings round the arc. The output pulses from the Geiger-tube are passed through scaling circuits and are made to actuate an electro-mechanical counter from which the intensities can be read directly. A strictly conventional application of the instrument would necessitate the scanning of two X-ray diffraction lines, one from the anatase pattern and one from the rutile pattern, and a subsequent comparison of the ratio of the integrated intensities or the peak heights of the two lines.In practice, however, the regulation of the instrument even with a voltage stabiliser in the mains supply, was not sufficient to give the desired reproducibility; also such a procedure would be too lengthy. It was found advantageous to open the receiving slit so that it subtended an angle of 2" at the centre of rotation of the specimen, an angle wide enough to take the whole of the diffracted beam simultaneously. This had the effect of increasing the accuracy of count of the weaker intensities and also allowed an alternate count to be made on either line in reasonably short periods. Each of the rutile 110 and anatase 101 lines was counted for 1 minute alternatively, three times over, and the total time of estimation was about 7 minutes.The alternation helped to eliminate longer period variations in the intensity of the primary X-ray beam. It would be more desirable to use two Geiger-tubes and to count the two lines simultaneously as was done by Richmond and 99 * 99 I 97 97 Fig. 5. Reproducibility of Geiger-counter X-ray spectrometer method Watson? They, however, used narrow slits and effectively measured peak heights; the present arrangement with wide slits effectively measures integrated intensities. The advantage of the former arrangement is in the tolerance of impurities allowed, provided the foreign material does not diffract at a Bragg angle identical with that of the chosen rutile or anatase line.The latter arrangement allows for variations in diffraction line contours brought about by lattice strain or small crystallite size, and bearing in mind pigmentary titanium dioxide which has an average crystallite size of about 0.2 p, it can be seen that wide slits have their own advantageous field of application. As in the previous method, standard rutile - amatase mixtures were prepared and used t o provide a calibration curve. The calibration wa:s checked daily at two points, and Fig. 5 illustrates the reproducibility of the method as the daily estimate of a 98.0 per cent. rutile standard over 139 consecutive days. The mean value of the 139 estimates was 97.9 per cent. of rutile with a standard deviation of 0-4 per cent. ; ithis deviation arose from all irregularities inherent in the method, such as sampling, operational faults and fluctuations of count. It was found to be essential to make the daily check cm two standards, not only to verify that the instrument had developed no fault but also because of long period variations which necessitated recalibration.In general, the instrument was recalibrated when the average of the previous six daily estimates differed from the: standard value by more than k0.5 per cent. Errors arising from non-uniformity in specimen preparation were found to be quite small, as the figures in Table I show. The volume of the specimen holder was 0.34m1, and by deliberately packing this volume under different pressures, specimen densities of between 1.03 g per ml and 1-50 g per ml were obtained.It is instructive to consider these results in relation to the fluctuations inherent in a relatively short period measurement with a Geiger-counter tube. When a beam of X-raysApril, 19521 ANALYSIS OF CRYSTALLINE POWDERS 183 of constant intensity is being measured by a Geiger-counter, the X-ray quanta arrive in a random fashion, and repetitive counts made for a given period of time will in general, be different. It can be shown6 that if +i is the true mean value of the count in the given time, TABLE I EFFECT OF SPECIMEN DENSITY Standard value 97.8 per cent. rutile 3 minute count A c \ Rutile Anatase Ti02, density, 110, R 101, A R/A Rutile, g g per ml Yo 0.349 1-03 1885 x 16 563 x 16 3.35 97.5 0.401 1.18 1992 x 16 595 x 16 3.35 97.5 0.422 1.24 2024 x 16 599 x 16 3.37 97.6 0.510 1.50 1852 x 16 569 x 16 3-26 96.8 f-e Weight of Specimen as determined by a very long period measurement, and if a large number of counts over the given time be made, values of n will be obtained distributed about the mean value +i according to Poisson’s law, (IT) ne-.n ! P, = - where P, is the probability or relative frequency of a count of n. The standard deviation of this distribution is 0 = (Z)* and, expressed as a percentage of the true mean, is given by 100(+i)* 100 ii (+ips -=- If n is not too small this becomes approximately lOO/(n)) and the accuracy increases with the time of the count. With a pigment that is substantially anatase the cohnt in 3 minutes on the rutile 110 line is approximately 9000 and on the anatase 101 line approximately 55,000.The standard deviations in repeated 3-minute counts are therefore 1.06 per cent. and 0.43 per cent. of the respective means. This accuracy was considered adequate for our purposes and, as shown below, leads to a standard deviation of less than 1 per cent. in the estimations of the percentage of rutile in a pigment. The form of the calibration curve for the percentage of rutile plotted against the ratio NR/N,, where NR is the rutile 110 count and N, is the anatase 101 count, fits the theoretical curve given by a + xR Y = b + (1 - x)A sufficiently well for an estimate of the accuracy of the method to be attempted. In this relationship Y is the ratio of the rutile 110 count to the anatase 101 count, a and b are the background contributions to the rutile 110 and anatase 101 intensities (independent of x ) , R and A are the counts from pure rutile and anatase, respectively, less the background, and x is the fraction of rutile.The relative values of R, A, a and b as estimated from many measurements are- By differentiation, R -h 3.0, A rl: 4.0, a * b c 1.0. ax - Rb+RA+aA - _ a y (R + Ar)2 and when the above values are substituted these become and184: HUGHES AND SMITH : RAPID X-RAY QUANTITATIVE [Vol. 77 Now r = N,/N, where NR and NA are the respective counts on the rutile 110 and anatase 101 lines, -- & dNR-dN, -- so NR NA and 2.1 l r ax = (1 + 1.33~)- ($ - 2) where ax is the error in x due to the errors dNR and dN,. therefore the standard deviation of x is given by The standard deviations of N, and NA are however (NB)* and (NA)* respectively, Ax has been computed for values of x from 0 to 1.0 and plotted in Fig.6. With a pigment containing 98 per cent. of rutile the theoretical standard deviation in a large number of 0 50 Rutile, % 100 Fig. 6. Standard deviation of determination of 0 to 100 per cent. of rutile counts is 0.44 per cent., which compares well with the value of 0.4 per cent. found in practice (Fig. 51, and it can be assumed that the errors of estimation are almost entirely due to the random nature of the diffracted X-ray beam, and that errors due to experimental variations in this method are of a different order. By taking longer counts the accuracy can be increased until the experimental variations become significant.The accuracy is dependent on the sensitivity of the Geiger-counter tube and if the latter is moved in its seating or replaced, a new calibration is necessary. It should be pointed out that the high standard of accuracy attainable by this method is partly the result of the uniform and ideal nature of the titanium dioxide powders used. The pigments consist of crystallites which are remarkably uniform in size; their mean size is about 0.2 p and standard deviation about 0.05 p, SO no coniplications owing to secondary extinction arise. When materials are used that contain coarser crystallites > 1 p, the estimations may be out by several per cent., and it cannot be: over-emphasised that high accuracy is only attainable when dealing with powders of uniform quality.Finally, some mention should be made of the standard mixtures of rutile and anatase pigments on which the absolute accuracy of the estimations depends, In general, all the titanium dioxide produced in the pigment industry has undergone relatively severe thermal treatment in the form of high temperature calcination at 800" to 1000" C, and consequentlyApril, 19521 ANALYSIS OF CRYSTALLINE POWDERS 185 anatase pigments, which are metastable with respect to rutile, usually contain a small percentage of rutile. Likewise, rutile pigments, which are usually manufactured by the high temperature transformation of anatase titanium dioxide, generally contain a residual amount of anatase. Under these circumstances it is necessary to use a method of successive approximations, to make an estimate of the absolute rutile content of the two pigments used to prepare the standards. The two pigments, which are substantially rutile and anatase, are first assumed t o be 100 per cent.in their respective crystalline forms. Standard mixtures are made up and accurate counts taken on the rutile 110 and anatase 101 lines. These counts are plotted against the apparent percentage of rutile in the standards. The background under the respective lines is found by interpolation of background counts outside and between the lines. All intensities are expressed as fractions of the rutile 110 background which is given the arbitrary value 1. The two primary pigments both show counts in the position of the minor constituent line greater than the interpolated background count. It is possible to deduce the residual percentages in the primary pigments from the difference between the count on the minor constituent line and the interpolated background count taken in conjunction with the slope of counts against apparent percentage of rutile curves. These curves are linear over the ranges 0 to 10 per cent. of rutile and 90 to 100 per cent. of rutile, and the corrections are applied to make the linear extrapolation of the new curves to 100 per cent. of rutile and 100 per cent. of anatase coincide with the respective background values. REFERENCE s 1. 2. 3. 4. 5. 6. BRITISH TITAN PRODUCTS Co. LTD. BILLINGHAM, Co. DURHAM Rooksby, H. P., Analyst, 1945, 70, 166. Brentano, J. C. M., Z . Phys., 1931, 70, 74; Proc. Phys. SOC., Lond., 1935, 47, 932. Bleeksma, J., Kloos, G., and di Giovanni, H. J., Philips Tech. Rev., 1948, 10, 1. Lonsdale, K., Acta Crystall., 1948, 1, 12. Richmond, J. T., and Watson, P. E., J . Oil Col. Chem. Ass., 1952, 35, 162. Bateman, H., Phil. Mag., 1910, 20, 704. RESEARCH DEPARTMENT

ISSN:0003-2654    

DOI:10.1039/AN9527700179

出版商:RSC    

年代:1952

数据来源: RSC