- Email: [email protected]
SEVERE COMBINED IMMUNODEFICIENCY AND ADENOSINE-DEAMINASE DEFICIENCY
1217 that beset our world, we can, at least, grant the oppressed the small comfort that is theirs if their plight is at least not
denied. Coney Island Hospital, 2601 Ocean Parkway, Brooklyn, New York 11235, U.S.A.
SEYMOUR M. GLICK.
"
*** The remark Not too much sign there of an oppressive and restrictive regime " has been taken too literally and used to place this journal in a position it has never occupied, as Dr Glick will see if he refers to two earlier editorials.·2
Our latest editorial was an attempt to the other side of the argument on Soviet psychiatry. 70,000 is at least better than nothing.-ED. L. extract
FLUORIDE TOXICITY
SIR,-Your editorial (Oct. 20, p. 889) suggests that the case for fluoridation has never been adequately documented. There must in fact be few subjects which are better documented in the world literature. The Kettering Abstracts on Inorganic Fluorides issued by the University of Cincinnati summarises every publication of substance and extends now to many thousands of abstracts. The impormaterial is assembled in works of reference such as Hodge and Smith’s Fluorine Chemistryand the W.H.O. Monograph on Fluorides and Human Health,4 and doubts such as those mentioned in your editorial have been examined and shown to be without substance in the reports of the various official committees and commissions of inquiry which have from time to time been held in various parts of the world. Thus the report of the Tasmanian Royal Commission on the Fluoridation of Public Water Supplies5 is a particularly useful document. For those who have not the time to study the subject in such depth, the information in the Reports on the Fluoridation Studies 6,7 issued by this Department and the document of Questions and Answers issued by the British Dental Association8 are useful. As is inevitable in all medical and scientific subjects, a few research-workers will be found who hold views differing from the general consensus of scientific opinion, and their evidence must always be carefully assessed. Most of the doubts on fluoridation expressed by members of the general public arise from ill-founded statements in the various publications of the anti-fluoridation organisations.
tant
Department of Health and Social Security, Alexander Fleming House,
G. E. GODBER,
London SE1.
Chief Medical Officer.
CHLORAMPHENICOL
SIR,-In their report on indications and warning about chloramphenicol, Mr Dunne and his colleagues (Oct. 6, p. 781) indicated that the International Organisation of Consumers Unions is interested in the indications and sideeffects of drugs. We wholeheartedly approve this attitude, since adverse reaction to drugs is a growing problem the world over, underrated by many doctors. As our country was not 1. Lancet, 1971, ii, 1361. 2. ibid. 1972, ii, 1237. 3. Hodge, H. C., Smith, F. A. Fluorine Chemistry (edited by J. H. Simmons); vol. 4. New York, 1965. 4. Monograph Ser. W.H.O. no. 59. 1972, Geneva. 5. Government of Tasmania. Report of the Royal Commission into the Fluoridation of Public Water Supplies, 1968. 6. Rep. publ. Hlth med. Subj., no. 105. 1962. 7. ibid. no. 122. 1969. 8. British Dental Association. Fluoridation of Water Supplies: Questions and Answers. London, 1969.
included in the international survey, one could assume that chloramphenicol is not indiscriminately recommended In Belgium, chloramphenicol or misused, which is not so. is still being prescribed in instances in which it offers no serious advantages over safer drugs. As hasmatologists we have had in recent years knowledge of four chloramphenicol" aplastic-anxmia patients who were treated in the University Hospital and who died. In each instance the drug was given for unjustified indications: (1) bronchitis in a 20-year-old athlete before a competition, (2) a 16-year-old girl wrongly suspected of " criminal" abortion, (3) an older patient needing the " cheapest " drug for an acute otitis media, (4) a 35-year-old woman treated for angina. We strongly feel that some more stringent action has to be taken to prevent such tragic events. In this context attention should be drawn to the widespread use of other than Parke Davis brands of chloramphenicol, using unconnected brand names. Besides the four brands mentioned by Dunne et al., a fifth brand is sold in some E.E.C. countries : ’Proterciclina’ (Laboratori Pro-ter, Milano, Italy, and Chemielux, Luxembourg). The main problems with proterciclina are: (1) the carton of the oral form does not mention the true nature of proterciclina (thus this drug tends to be confused with safe antibiotics); (2) the leaflet mentions that this drug is a chemical combination of chloramphenicol and tetracycline and wrongly claims that, due to the lower dosage, the danger of complication is decreased (the risk of chloramphenicol aplastic anxmia is not dose-related). We entirely agree with the recommendations suggested by the Research Institute for Consumer Affairs. One more recommendation is being proposed: any brand should clearly mention the true chemical nature of the drug under a name familiar to all practitioners. "
Department of Medical Research, University of Leuven, 3000 Leuven, Belgium.
R. L. VERWILGHEN M. VERSTRAETE.
SEVERE COMBINED IMMUNODEFICIENCY AND ADENOSINE-DEAMINASE DEFICIENCY
SIR,-A syndrome of severe combined immunodeficiency has been reported in association with an absence of the enzyme red-cell adenosine deaminase.1-3 Previous evidence indicated that accurate prenatal diagnosis might not be feasible in this disorder, since the red-cell isozymes of adenosine deaminase, thought to be controlled at a separate genetic locus from the tissue isozyme, were very often not expressed by normal fibroblasts in tissue cultures. However, we have lately determined that fibroblasts as well as tissues from one of these patients are deficient not only in the red-cell enzyme but also in the " tissue " isozymes of adenosine deaminase.5 We have performed enzyme assays by three separate methods,6-8 as well as zymograms on starch gel,7 on three fibroblastic amniotic-cell cultures derived from pregnancies not at risk for immunodeficiency diseases. As shown in the table, enzyme assays demonstrated activity similar to or higher than that of normal fibroblasts. The zymogram demon1. 2. 3.
4. 5. 6. 7. 8.
Giblett, E., Anderson, J., Cohen, F., Pollara, B., Meuwissen, H. J. Lancet, 1972, ii, 1067. Dissing, J., Knudsen, B. ibid. p. 1316. Ochs, H. H., Yount, J. E., Giblett, E. R., Chen, S. H., Scott, C. R., Wedgwood, R. J. ibid. 1973, i, 1393. Edwards, Y. H., Hopkinson, D. A., Harris, H. Ann. hum. Genet. 1971, 35, 207. Hirschhorn, R., Levytska, V., Pollara, B., Meuwissen, H. Unpublished. Goldberg, D. M. Br. med. J. 1965, i, 353. Spencer, N., Hopkinson, D. A., Harris, H. Ann. hum. Genet. 1968, 32, 9. Hirschhorn, R. Unpublished.
1218 have noticed these significant physical it worth placing them on record.
strated that this
activity was due to isozymes identical in mobility to those found in normal skin fibroblasts, including both the red-cell and tissue type. While examining the zymograms, we found differing ratios of the red-cell and tissue isozymes in different amniotic cultures, as previously reported in skin fibroblasts. In several fibroblast and amniotic cultures of normal individuals the red-cell Similar variation in the not be detected. ratio of these isozymes has been found in lymphocytes.8 However, the absence of both types of isozyme in the fibroblasts and other tissues of an affected child imply CELLS AND FIBROBLASTS
(mjjLM
per mg.
protein
per
min.)
but I
thought
St. Mary’s Hospital, 14
Pope’s Lane,
K. HAZELL.
Colchester CO3 3JL.
In
isozyme could
ADENOSINE-DEAMINASE ACTIVITY OF CULTURED HUMAN AMNIOTIC
signs,
England Now
The trauma of selling up my house was lessened by with the boys who were running the truck for the auction-rooms. They were young, and they worked hard, on a warm afternoon, refusing tea until all was loaded. The bouncing one in charge turned out to be a science graduate, a professor’s son; his mate had a pensive personality, with Celtic sadness. They cleared the last lot. tinged " That everything ?" asked the pensive one. Yes, thank you, that’s all ", I said. " No T.v. ?" he queried, " No, I don’t have one." " You mean you don’t have one ? How come ?" " I just don’t watch T.v. I don’t enjoy it ", I urged me to self-defence. " It’s not replied. Their gaze real ", I said. " Life isn’t like that. T.v. is phoney." " What is reality ?" asked the pensive one searchingly. " Now that is a hard one. I’d have to take time to think up the answer to that. All I can tell you is that when you’re as old as I am you’ll know what reality is. I guess I’m the T.v. in this house !" They relaxed, heartily enjoying their tea. The drop cookies I had made in order to empty out the cupboards went over well. " Did you make these ?" Their surprise now had more approval in it. I felt I had turned a corner. It all came back to me yesterday when I said that no, I wasn’t going to watch the royal wedding on T.v. My friend, enjoying four separate invitations to watch it in colour, couldn’t quite see my point of view-that it wasn’t real. If I could watch the actual thing, I would like to see it. But I don’t want to see it on T.v. More and more the media have become art forms. Reality is presented as a picturein verbal or visual or sound images. It is an arrangement, a composition. Art is displacing objectivity. It is not that I am immune to art; but when I want to know what is happening, I want to know the reality. How would you define reality ? It must include birth and death, and all that goes along the way-like selling up your house, and moving, and meeting real people. contact
"
* Method 1 is that of Spencer et al.’ at 27°C. Method 2 is an adaptation of the method of Spencer et al., in which the reaction mixture is incubated for 1 hour at 37 °C before determination of inosine present. Method 3 is that of Goldberg but at a substrate concentration of 25 mg. per 100 ml.
that the active enzyme molecule responsible for the activity of both types of isozyme is coded by the same gene. The lower-molecular-weight red-cell isozyme can be converted to a higher-molecular-weight set of tissue isozymes,8 each organ-specific in its electrophoretic mobility. This is probably due to the conversion factors described
previously.9 These findings make it highly likely that accurate prenatal diagnosis of this newly described fatal disease will be feasible with a combination of enzyme assay and starch-gel zymograms. Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, N.Y. 10016. Department of Pediatrics,
ROCHELLE HIRSCHHORN.
Mount Sinai School of
Medicine, New York, N.Y., U.S.A.
*
NICHOLAS G. BERATIS.
*
ON A DISTANT PROSPECT OF THE ROYAL
ABO, Rh., forget: You’ll need a different alphabet. Mind your " p "s and " q "sand " t ", Cross-cheque with chi-square for your Fee. Test failed, if once you lose your nerve Through Errors in the Normal Curve. Candidates who think Regression’s Back to Kid’s stuff-try next session! Censors now will look askance At those who baulk at Variance. So be sure you know no less Of sweet F(a) than J. F. S.! Ex- " STUDENT."
patients have it in an ordinary geriatric ward. Naturally, confirmation requires radiological examination, but it can be and has been diagnosed by physical signs in the lungs. There can be various degrees of dullness on percussion at the base of the lungs-not in keeping with pleural effusion, bronchopneumonia, or simple collapsebut the significant sign is moderate dullness when the stomach is full after a meal, alternating with normal resonance when the stomach is empty. The signs therefore
Nishihara, H., Ishikawa, S., Shinkai, K., Akedo, H. Biochim. biophys. Acta, 1973, 302, 492.
warning!
Lucubrate until the morning: But swot not with weary eyes On tomes of Cecil, Pappworth, Price. Read up Fisher (R.A.), Hilln’s now mightier than the pill.
SiR,-After decades one would envisage that the ordinary medical textbooks would, by now, have left no diagnostic clinical sign unrecorded. But as regards diaphragmatic hiatus hernia this appears to be not so. True, some of the signs in the lungs in this condition are touched upon very scantily. Hiatus herniation of the stomach into the chest, however, is common in the elderly and usually one or more
9.
COLLEGE*
Would-be Members, heed this
A CLINICAL SIGN IN HIATUS HERNIA
vary from time to time. When the stomach is full of gas borborygmi may also be heard. No doubt other physicians
*
...
.
Prompted by a letter from J. F. S. (Nov. 17, p. 1149) warning prospective candidates for the M.R.c.P.(u.x.) examination that they will in future need to demonstrate an acquaintance with the principles of elementary statistics.
denied. Coney Island Hospital, 2601 Ocean Parkway, Brooklyn, New York 11235, U.S.A.
SEYMOUR M. GLICK.
"
*** The remark Not too much sign there of an oppressive and restrictive regime " has been taken too literally and used to place this journal in a position it has never occupied, as Dr Glick will see if he refers to two earlier editorials.·2
Our latest editorial was an attempt to the other side of the argument on Soviet psychiatry. 70,000 is at least better than nothing.-ED. L. extract
FLUORIDE TOXICITY
SIR,-Your editorial (Oct. 20, p. 889) suggests that the case for fluoridation has never been adequately documented. There must in fact be few subjects which are better documented in the world literature. The Kettering Abstracts on Inorganic Fluorides issued by the University of Cincinnati summarises every publication of substance and extends now to many thousands of abstracts. The impormaterial is assembled in works of reference such as Hodge and Smith’s Fluorine Chemistryand the W.H.O. Monograph on Fluorides and Human Health,4 and doubts such as those mentioned in your editorial have been examined and shown to be without substance in the reports of the various official committees and commissions of inquiry which have from time to time been held in various parts of the world. Thus the report of the Tasmanian Royal Commission on the Fluoridation of Public Water Supplies5 is a particularly useful document. For those who have not the time to study the subject in such depth, the information in the Reports on the Fluoridation Studies 6,7 issued by this Department and the document of Questions and Answers issued by the British Dental Association8 are useful. As is inevitable in all medical and scientific subjects, a few research-workers will be found who hold views differing from the general consensus of scientific opinion, and their evidence must always be carefully assessed. Most of the doubts on fluoridation expressed by members of the general public arise from ill-founded statements in the various publications of the anti-fluoridation organisations.
tant
Department of Health and Social Security, Alexander Fleming House,
G. E. GODBER,
London SE1.
Chief Medical Officer.
CHLORAMPHENICOL
SIR,-In their report on indications and warning about chloramphenicol, Mr Dunne and his colleagues (Oct. 6, p. 781) indicated that the International Organisation of Consumers Unions is interested in the indications and sideeffects of drugs. We wholeheartedly approve this attitude, since adverse reaction to drugs is a growing problem the world over, underrated by many doctors. As our country was not 1. Lancet, 1971, ii, 1361. 2. ibid. 1972, ii, 1237. 3. Hodge, H. C., Smith, F. A. Fluorine Chemistry (edited by J. H. Simmons); vol. 4. New York, 1965. 4. Monograph Ser. W.H.O. no. 59. 1972, Geneva. 5. Government of Tasmania. Report of the Royal Commission into the Fluoridation of Public Water Supplies, 1968. 6. Rep. publ. Hlth med. Subj., no. 105. 1962. 7. ibid. no. 122. 1969. 8. British Dental Association. Fluoridation of Water Supplies: Questions and Answers. London, 1969.
included in the international survey, one could assume that chloramphenicol is not indiscriminately recommended In Belgium, chloramphenicol or misused, which is not so. is still being prescribed in instances in which it offers no serious advantages over safer drugs. As hasmatologists we have had in recent years knowledge of four chloramphenicol" aplastic-anxmia patients who were treated in the University Hospital and who died. In each instance the drug was given for unjustified indications: (1) bronchitis in a 20-year-old athlete before a competition, (2) a 16-year-old girl wrongly suspected of " criminal" abortion, (3) an older patient needing the " cheapest " drug for an acute otitis media, (4) a 35-year-old woman treated for angina. We strongly feel that some more stringent action has to be taken to prevent such tragic events. In this context attention should be drawn to the widespread use of other than Parke Davis brands of chloramphenicol, using unconnected brand names. Besides the four brands mentioned by Dunne et al., a fifth brand is sold in some E.E.C. countries : ’Proterciclina’ (Laboratori Pro-ter, Milano, Italy, and Chemielux, Luxembourg). The main problems with proterciclina are: (1) the carton of the oral form does not mention the true nature of proterciclina (thus this drug tends to be confused with safe antibiotics); (2) the leaflet mentions that this drug is a chemical combination of chloramphenicol and tetracycline and wrongly claims that, due to the lower dosage, the danger of complication is decreased (the risk of chloramphenicol aplastic anxmia is not dose-related). We entirely agree with the recommendations suggested by the Research Institute for Consumer Affairs. One more recommendation is being proposed: any brand should clearly mention the true chemical nature of the drug under a name familiar to all practitioners. "
Department of Medical Research, University of Leuven, 3000 Leuven, Belgium.
R. L. VERWILGHEN M. VERSTRAETE.
SEVERE COMBINED IMMUNODEFICIENCY AND ADENOSINE-DEAMINASE DEFICIENCY
SIR,-A syndrome of severe combined immunodeficiency has been reported in association with an absence of the enzyme red-cell adenosine deaminase.1-3 Previous evidence indicated that accurate prenatal diagnosis might not be feasible in this disorder, since the red-cell isozymes of adenosine deaminase, thought to be controlled at a separate genetic locus from the tissue isozyme, were very often not expressed by normal fibroblasts in tissue cultures. However, we have lately determined that fibroblasts as well as tissues from one of these patients are deficient not only in the red-cell enzyme but also in the " tissue " isozymes of adenosine deaminase.5 We have performed enzyme assays by three separate methods,6-8 as well as zymograms on starch gel,7 on three fibroblastic amniotic-cell cultures derived from pregnancies not at risk for immunodeficiency diseases. As shown in the table, enzyme assays demonstrated activity similar to or higher than that of normal fibroblasts. The zymogram demon1. 2. 3.
4. 5. 6. 7. 8.
Giblett, E., Anderson, J., Cohen, F., Pollara, B., Meuwissen, H. J. Lancet, 1972, ii, 1067. Dissing, J., Knudsen, B. ibid. p. 1316. Ochs, H. H., Yount, J. E., Giblett, E. R., Chen, S. H., Scott, C. R., Wedgwood, R. J. ibid. 1973, i, 1393. Edwards, Y. H., Hopkinson, D. A., Harris, H. Ann. hum. Genet. 1971, 35, 207. Hirschhorn, R., Levytska, V., Pollara, B., Meuwissen, H. Unpublished. Goldberg, D. M. Br. med. J. 1965, i, 353. Spencer, N., Hopkinson, D. A., Harris, H. Ann. hum. Genet. 1968, 32, 9. Hirschhorn, R. Unpublished.
1218 have noticed these significant physical it worth placing them on record.
strated that this
activity was due to isozymes identical in mobility to those found in normal skin fibroblasts, including both the red-cell and tissue type. While examining the zymograms, we found differing ratios of the red-cell and tissue isozymes in different amniotic cultures, as previously reported in skin fibroblasts. In several fibroblast and amniotic cultures of normal individuals the red-cell Similar variation in the not be detected. ratio of these isozymes has been found in lymphocytes.8 However, the absence of both types of isozyme in the fibroblasts and other tissues of an affected child imply CELLS AND FIBROBLASTS
(mjjLM
per mg.
protein
per
min.)
but I
thought
St. Mary’s Hospital, 14
Pope’s Lane,
K. HAZELL.
Colchester CO3 3JL.
In
isozyme could
ADENOSINE-DEAMINASE ACTIVITY OF CULTURED HUMAN AMNIOTIC
signs,
England Now
The trauma of selling up my house was lessened by with the boys who were running the truck for the auction-rooms. They were young, and they worked hard, on a warm afternoon, refusing tea until all was loaded. The bouncing one in charge turned out to be a science graduate, a professor’s son; his mate had a pensive personality, with Celtic sadness. They cleared the last lot. tinged " That everything ?" asked the pensive one. Yes, thank you, that’s all ", I said. " No T.v. ?" he queried, " No, I don’t have one." " You mean you don’t have one ? How come ?" " I just don’t watch T.v. I don’t enjoy it ", I urged me to self-defence. " It’s not replied. Their gaze real ", I said. " Life isn’t like that. T.v. is phoney." " What is reality ?" asked the pensive one searchingly. " Now that is a hard one. I’d have to take time to think up the answer to that. All I can tell you is that when you’re as old as I am you’ll know what reality is. I guess I’m the T.v. in this house !" They relaxed, heartily enjoying their tea. The drop cookies I had made in order to empty out the cupboards went over well. " Did you make these ?" Their surprise now had more approval in it. I felt I had turned a corner. It all came back to me yesterday when I said that no, I wasn’t going to watch the royal wedding on T.v. My friend, enjoying four separate invitations to watch it in colour, couldn’t quite see my point of view-that it wasn’t real. If I could watch the actual thing, I would like to see it. But I don’t want to see it on T.v. More and more the media have become art forms. Reality is presented as a picturein verbal or visual or sound images. It is an arrangement, a composition. Art is displacing objectivity. It is not that I am immune to art; but when I want to know what is happening, I want to know the reality. How would you define reality ? It must include birth and death, and all that goes along the way-like selling up your house, and moving, and meeting real people. contact
"
* Method 1 is that of Spencer et al.’ at 27°C. Method 2 is an adaptation of the method of Spencer et al., in which the reaction mixture is incubated for 1 hour at 37 °C before determination of inosine present. Method 3 is that of Goldberg but at a substrate concentration of 25 mg. per 100 ml.
that the active enzyme molecule responsible for the activity of both types of isozyme is coded by the same gene. The lower-molecular-weight red-cell isozyme can be converted to a higher-molecular-weight set of tissue isozymes,8 each organ-specific in its electrophoretic mobility. This is probably due to the conversion factors described
previously.9 These findings make it highly likely that accurate prenatal diagnosis of this newly described fatal disease will be feasible with a combination of enzyme assay and starch-gel zymograms. Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, N.Y. 10016. Department of Pediatrics,
ROCHELLE HIRSCHHORN.
Mount Sinai School of
Medicine, New York, N.Y., U.S.A.
*
NICHOLAS G. BERATIS.
*
ON A DISTANT PROSPECT OF THE ROYAL
ABO, Rh., forget: You’ll need a different alphabet. Mind your " p "s and " q "sand " t ", Cross-cheque with chi-square for your Fee. Test failed, if once you lose your nerve Through Errors in the Normal Curve. Candidates who think Regression’s Back to Kid’s stuff-try next session! Censors now will look askance At those who baulk at Variance. So be sure you know no less Of sweet F(a) than J. F. S.! Ex- " STUDENT."
patients have it in an ordinary geriatric ward. Naturally, confirmation requires radiological examination, but it can be and has been diagnosed by physical signs in the lungs. There can be various degrees of dullness on percussion at the base of the lungs-not in keeping with pleural effusion, bronchopneumonia, or simple collapsebut the significant sign is moderate dullness when the stomach is full after a meal, alternating with normal resonance when the stomach is empty. The signs therefore
Nishihara, H., Ishikawa, S., Shinkai, K., Akedo, H. Biochim. biophys. Acta, 1973, 302, 492.
warning!
Lucubrate until the morning: But swot not with weary eyes On tomes of Cecil, Pappworth, Price. Read up Fisher (R.A.), Hilln’s now mightier than the pill.
SiR,-After decades one would envisage that the ordinary medical textbooks would, by now, have left no diagnostic clinical sign unrecorded. But as regards diaphragmatic hiatus hernia this appears to be not so. True, some of the signs in the lungs in this condition are touched upon very scantily. Hiatus herniation of the stomach into the chest, however, is common in the elderly and usually one or more
9.
COLLEGE*
Would-be Members, heed this
A CLINICAL SIGN IN HIATUS HERNIA
vary from time to time. When the stomach is full of gas borborygmi may also be heard. No doubt other physicians
*
...
.
Prompted by a letter from J. F. S. (Nov. 17, p. 1149) warning prospective candidates for the M.R.c.P.(u.x.) examination that they will in future need to demonstrate an acquaintance with the principles of elementary statistics.