- Email: [email protected]
PIGEONS
154 We therefore concur with the suggestion that hypermethioninaemia in these circumstances can be attributed primarily to severe loss of functioning hepatic tissue and is not likelv to indicate an inborn error of methionine metabolism. C. R. SCRIVER deBelle Laboratory for Biochemical Genetics, C. L. CLOW Montreal Children’s Hospital, M. SILVERBERG. Montreal 25, Quebec.
TABLE II-CHROMIUM
REACTIONS OF ABNORMAL SERA
JELLIFICATION
139
NORMAL AND
JELLIFICATION REACTION SIR,-Dr. Cohen reported1 that sera containing paraproteins, found in multiple myeloma and Waldenstrom’s disease, form a gel with high concentrations of chromium salts in saline solution, while normal sera, and hyperproteinsemic sera without paraproteins do not. He suggested the use of a 10% (0-37M) solution of chromium chloride (CrC1a, 6H2O) as a screening test for paraproteinsemia. I have evaluated Dr. Cohen’s technique on 139 sera submitted to our reference service for immunoelectrophoretic analysis (I.E.P.A.). Diagnoses supplied by the clinicians and results of the I.E.P.A. are sumCHROMIUM
TABLE I-CLINICAL AND I.E.P.A. INFORMATION ON THE TESTED
139
*
SERA
light-chain type. Four chromium-positive and six chromiumnegative sera were typed by i.E.P.A. using specific anti-x and anti-X sera (Hyland Laboratories). No correlation was found. From these findings, I conclude that the chromium jellification reaction is not a reliable screening test for paraproteintmia, National Reference Laboratory, Canadian Red Cross Blood Transfusion Service, Toronto, Ontario, Canada.
CECILE A. LOVETT.
PIGEONS
Cryptococcus neoformans 1 requires, I think, some amplification. Most racing-pigeon fanciers are very conscious of the public-health problem and willing to SiR,-Your reference
* 8 other were
in which the immunoelectrophoretic pattern was equivocal eliminated from the series and from this tabulation; all reacted
sera
negatively.
marised in table I. All sera classed as paraproteinxmias for this study contained abnormal immunoglobulins demonstrable
by
I.E.P .A.
Chromium jellification
was tested at three concentrations of CrCLg (Analar)-namely, 2%, 5%, and 10%. Tests were performed at room temperature (22±2’C) in 10 x 75 mm. tubes, using 0-2 ml. of serum and 0-075 ml. of CrCl3 solution. A solid gel which could not be dislodged by inverting the tube was read as a positive reaction. Preliminary tests showed that, while some sera formed a solid gel almost immediately, others reacted more slowly. Tests were therefore read after 24 hours. Results are summarised in table II. Although the sera had been stored at -20°C for up to 21/2 years, both positive and negative results were obtained with sera of all ages. Four serum samples from the same patient, stored for from 5 days to 21/2 years, gave identical positive reactions. I feel therefore that ageing is not responsible for the " false negative " results that I found. 5 sera known to contain paraproteins but reacting negatively to 5% and 10% solutions of CrCl3 were also tested with 6% and 8% solutions. All reactions remained negative. The presence of 0-1% of the sodium salt of edetic acid did not affect the reactions. 11 abnormal, but no normal, sera reacted negatively to 2%, 5%, and 10% concentrations of CrCla. No explanation has been found. No correlation was observed between the class of abnormal immunoglobulin (IgG, IgA, and IgM) present and the reaction
pattern. It is
generally accepted that paraproteins, unlike normal immunoglobulins, contain only one type of light-chain. An
attempt
was
made to correlate the reaction patterns with the 1. Cohen, H. A. Lancet, 1965, i, 1302.
to
cooperate in any reasonable scheme. The " feud " at Harlow is because of the indiscriminate destruction of pigeons and the danger that a proportion of these may be stray racers, though admittedly probably valueless for racing purposes. The opposition is partly on humanitarian grounds, but also because a racing pigeon is protected under an Act originally intended to help the feudal lord of the manor against his serfs. Many feel that if fanciers condone this random slaughter they will weaken their legal position when it comes to cases of the wanton shooting of birds in flight. Their willing cooperation could be obtained if a formula can be found so that legal protection is not endangered. In many cities they cooperate with the authorities in trapping and the use of non-lethal
drugs. Our particular concern is to try and educate both the general public and health authorities in the difference between racing pigeons and street pigeons-while both are ultimately descended from the rock dove, the conditions in which they live gives rise
substantial differences in risk from disease. It is very for the spores of C. neoformans to become apparent until the droppings have remained some time; although there is some evidence that the spores develop more rapidly than was thought in the past, there is a world of difference between a pigeon-loft regularly cleaned out at least once a week, and the attic of a bombed building undisturbed for months. Unfortunately the published reports only too frequently fail to distinguish between the different habitats, and what is theoretically possible is confused with what is probable. The same reasoning applies to ornithosis and other chronic diseases; the rigorous selection of the racing programme soon eliminates those in the loft deficient in either health or ability, and therefore the racing-pigeon fancier is probably less liable to be associated with diseased birds than is the visitor to Trafalgar Square. I am perhaps over-simplifying the problem in an attempt to 1. Lancet, 1965, ii, 1335.
to very rare
155 get adequate consideration of the epidemiological conditions, but the problem is of major importance for pigeon-fanciers. This is not only because of their own health, but because some 35% of fanciers are tenants on local-authority estates; permission to keep pigeons is therefore subject to the opinions and prejudices of housing committees-and they, like so many others, can be misinformed. C. A. E. OSMAN 19, Doughty Street, Editor, The Racing Pigeon. London, W.C.1.
RENAL AUTOTRANSPLANTATION SIR,-Dr. Serrallach-Mila and his colleaguesmust surely be given the credit for first describing the treatment of renalartery stenosis by autotransplantation of the kidney to the iliac fossa. They were the first who actually did it, even if Mr. Dempster (Jan. 1) had suggested it before. This procedure seems to me a logical answer in certain cases where revascularisation of the kidney in its normal position is technically difficult. I have the impression that we shall be hearing more about this approach in the future. As Mr. Dempster points out, this form of autotransplantation of the kidney is also a solution to the problem of reestablishing ureteral continuity after injury or disease of a long segment of ureter. Hardy has reported a clinical case successfully treated by this method.2 The alternative of using intestine to bridge the gap may be more appealing to a greater number of surgeons with a different training, but this has the drawbacks of producing reflux, metabolic acidosis, and sometimes massive dilatation of the intestinal segment. General Hospital, Warrington, E. BENGOECHEA GONZALEZ. Lancashire.
ENZYMES IN DOWN’S SYNDROME SiR,-An increase of leucocyte alkaline phosphatase3 and
leucocyte glucose-6-phosphate dehydrogenase (G.-6-P.D.) 45 has been reported in patients with Down’s syndrome. We report here the activity of these two enzymes in the platelets of such patients. The platelets were prepared as described by Wurzel et al.B except that they were washed with 0-2% saline solution once to complete the destruction of erythrocytes, and lysis was carried out using saponin. G.-6-P.D. was assayed by the procedure of Kornberg and Horecker,’ and alkaline phosphatase by the method of Bessey et al.using p-nitrophenol phosphate as substrate at pH 9-3. There was no difference between the patients with Down’s syndrome and controls in G.-6-P.D. activity (expressed as platelet-count, or as protein content of nicotinamide-adenine dinucleotide phosphate [N.A.D.P.]) and alkaline-phosphatase activity, as follows (all values are expressed as mean standard error, and the numbers of subjects studied are given in parentheses):
quine-sensitive type of G.-6-P.D. deficiency, no abnormality in enzyme activity has been found in leucocytes 12 or fibroblasts 13 corresponding to the decrease seen in erythrocytes. Cox 14 reported that an extra chromosome 21 does not affect either the alkaline-phosphatase concentration or its mode of regulation in skin cultures derived from trisomic patients with Down’s syndrome. The failure to find an increase of either platelet alkaline phosphatase or platelet G.-6-P.D. in Down’s syndrome suggests that the increase in leucocyte alkaline phosphatase and leucocyte G.-6-P.D. probably represents not the direct action of a structural gene locus, but a more localised reaction. This would also provide further confirmation for the concept that platelets have a different origin from leucocytes and erythrocytes .15 We wish to thank Dr. N. Shahidi for his suggestions. These studies were supported by grants from the Illinois Mental Health Fund and the United States Public Health Service (TI-AM-5186). Children’s Memorial Hospital, and Department of Pediatrics, Northwestern University Medical School, Chicago.
LING-YU SHIH DAVID YI-YUNG HSIA.
NO CHARGE Sir,-I very surprised to read your annotation 16 about issued by general practitioners. prescriptions The implication of overprescribing by disillusioned doctors leaves a bitter taste in the mouth and must be far from the truth-except perhaps in some instances. At a time when critical negotiations are in progress to improve the National Health Service it is unwise to make damaging statements which could be detrimental to the profession. Let us face the facts-the public are conditioned to using free services, and, human nature being what it is, some people will quite naturally get all they can for nothing. This applies particularly to inadequate hypochondriacal personalities who constitute about 2% of every practice and are content to use their family doctor in the same way as they would a drug store. This 2% from each practice throughout the country, viewed collectively, represents a formidable destructive force within the N.H.S., and in the context of all the other social amenities and benefits which they astutely manoeuvre to their own advantage. This factor should be considered when planning future welfare schemes. GEORGE L. HINDSON. was
HELPING YOUR DOCTOR/PATIENT SIR,-It seems reasonable that, with so much recent publicity given to abuses of the National Health Service by patients, some efforts should be made to redress the balance. Two telephone calls from the daughter of a 66-year-old patient, a chronic and severe case of Parkinson’s disease, in the week before Christmas failed to produce a visit from the doctor. On Christmas Eve the patient fell, and a third phonecall finally brought the G.P. He left, leaving a Helping Your Doctor leaflet published by the Ministry of Health. Paragraphs 3 and 4 were marked, and the second half of the sentence in paragraph 3, pointing out that " Doctors are not under an obligation to see a patient just whenever and wherever the patient thinks fit ", was underlined. A final gesture was a note on the back of the leaflet: Please get your mother changed to another doctor." "
1.
2. 3. 4. 5. 6.
Serrallach-Mila, N., Paravisini, J., Mayol-Valls, P., Alberti, J., Casellas, A., Nolla-Panadés, J. Lancet, 1965, ii, 1130. Hardy, J. J. Am. med. Ass. 1963, 184, 97. Trubowitz, S., Kirman, D., Masek, B. Lancet, 1962, ii, 486. Mellman, W. J., Oski, F. A., Tedesco, T. A., Maciera-Coelho, A. Harris, H. ibid. 1964, ii, 674. Shih, L. Y., Wong, P., Inouye, T., Makler, M., Hsia, D. Y. Y. ibid. 1965, ii, 746. Wurzel, H., McCreary, T., Baker, L., Gumerman, L. Blood, 1961,
17, 314. Kornberg, A., Horecker, B. L. Meth. Enzym. 1955, 1, 323. Bessey, O. A., Lowry, O. H., Brock, M. J. J. biol. Chem. 1946, 164, 321. 9. Ramot, B., Fisher, S., Szeinberg, A., Adam, A., Chaim, S., Gafni, D. J. clin. Invest. 1959, 38, 2234. 10. Ramot, B., Szeinberg, A., Adam, A., Sheba, C., Gafni, D. ibid. p. 1659. 11. Gartler, S. M. Int. Congr. hum. Genet. 1961, 2, 622. 7. 8.
From this incident it appears that the Ministry have inadvertently provided general practitioners with a form, similar to that of a driving-test examiner, on which the appropriate
presumed faults in attitude of patients and their relatives
can
R. E. Nature, Lond. 1959,
183,
12. Marks,
P. A.,
Gross,
R.
T., Hurwitz,
1266.
Gartler, S. M. 4th Macy Conference on Genetics; p. 194. Ann Arbor, Michigan, 1964. 14. Cox, R. P. Expl Cell Res. 1965, 37, 690. 15. Saltzman, G. F. Acta med. scand. 1949, 132, suppl. 221. 16. Lancet, 1965, ii, 1172. 13.
TABLE II-CHROMIUM
REACTIONS OF ABNORMAL SERA
JELLIFICATION
139
NORMAL AND
JELLIFICATION REACTION SIR,-Dr. Cohen reported1 that sera containing paraproteins, found in multiple myeloma and Waldenstrom’s disease, form a gel with high concentrations of chromium salts in saline solution, while normal sera, and hyperproteinsemic sera without paraproteins do not. He suggested the use of a 10% (0-37M) solution of chromium chloride (CrC1a, 6H2O) as a screening test for paraproteinsemia. I have evaluated Dr. Cohen’s technique on 139 sera submitted to our reference service for immunoelectrophoretic analysis (I.E.P.A.). Diagnoses supplied by the clinicians and results of the I.E.P.A. are sumCHROMIUM
TABLE I-CLINICAL AND I.E.P.A. INFORMATION ON THE TESTED
139
*
SERA
light-chain type. Four chromium-positive and six chromiumnegative sera were typed by i.E.P.A. using specific anti-x and anti-X sera (Hyland Laboratories). No correlation was found. From these findings, I conclude that the chromium jellification reaction is not a reliable screening test for paraproteintmia, National Reference Laboratory, Canadian Red Cross Blood Transfusion Service, Toronto, Ontario, Canada.
CECILE A. LOVETT.
PIGEONS
Cryptococcus neoformans 1 requires, I think, some amplification. Most racing-pigeon fanciers are very conscious of the public-health problem and willing to SiR,-Your reference
* 8 other were
in which the immunoelectrophoretic pattern was equivocal eliminated from the series and from this tabulation; all reacted
sera
negatively.
marised in table I. All sera classed as paraproteinxmias for this study contained abnormal immunoglobulins demonstrable
by
I.E.P .A.
Chromium jellification
was tested at three concentrations of CrCLg (Analar)-namely, 2%, 5%, and 10%. Tests were performed at room temperature (22±2’C) in 10 x 75 mm. tubes, using 0-2 ml. of serum and 0-075 ml. of CrCl3 solution. A solid gel which could not be dislodged by inverting the tube was read as a positive reaction. Preliminary tests showed that, while some sera formed a solid gel almost immediately, others reacted more slowly. Tests were therefore read after 24 hours. Results are summarised in table II. Although the sera had been stored at -20°C for up to 21/2 years, both positive and negative results were obtained with sera of all ages. Four serum samples from the same patient, stored for from 5 days to 21/2 years, gave identical positive reactions. I feel therefore that ageing is not responsible for the " false negative " results that I found. 5 sera known to contain paraproteins but reacting negatively to 5% and 10% solutions of CrCl3 were also tested with 6% and 8% solutions. All reactions remained negative. The presence of 0-1% of the sodium salt of edetic acid did not affect the reactions. 11 abnormal, but no normal, sera reacted negatively to 2%, 5%, and 10% concentrations of CrCla. No explanation has been found. No correlation was observed between the class of abnormal immunoglobulin (IgG, IgA, and IgM) present and the reaction
pattern. It is
generally accepted that paraproteins, unlike normal immunoglobulins, contain only one type of light-chain. An
attempt
was
made to correlate the reaction patterns with the 1. Cohen, H. A. Lancet, 1965, i, 1302.
to
cooperate in any reasonable scheme. The " feud " at Harlow is because of the indiscriminate destruction of pigeons and the danger that a proportion of these may be stray racers, though admittedly probably valueless for racing purposes. The opposition is partly on humanitarian grounds, but also because a racing pigeon is protected under an Act originally intended to help the feudal lord of the manor against his serfs. Many feel that if fanciers condone this random slaughter they will weaken their legal position when it comes to cases of the wanton shooting of birds in flight. Their willing cooperation could be obtained if a formula can be found so that legal protection is not endangered. In many cities they cooperate with the authorities in trapping and the use of non-lethal
drugs. Our particular concern is to try and educate both the general public and health authorities in the difference between racing pigeons and street pigeons-while both are ultimately descended from the rock dove, the conditions in which they live gives rise
substantial differences in risk from disease. It is very for the spores of C. neoformans to become apparent until the droppings have remained some time; although there is some evidence that the spores develop more rapidly than was thought in the past, there is a world of difference between a pigeon-loft regularly cleaned out at least once a week, and the attic of a bombed building undisturbed for months. Unfortunately the published reports only too frequently fail to distinguish between the different habitats, and what is theoretically possible is confused with what is probable. The same reasoning applies to ornithosis and other chronic diseases; the rigorous selection of the racing programme soon eliminates those in the loft deficient in either health or ability, and therefore the racing-pigeon fancier is probably less liable to be associated with diseased birds than is the visitor to Trafalgar Square. I am perhaps over-simplifying the problem in an attempt to 1. Lancet, 1965, ii, 1335.
to very rare
155 get adequate consideration of the epidemiological conditions, but the problem is of major importance for pigeon-fanciers. This is not only because of their own health, but because some 35% of fanciers are tenants on local-authority estates; permission to keep pigeons is therefore subject to the opinions and prejudices of housing committees-and they, like so many others, can be misinformed. C. A. E. OSMAN 19, Doughty Street, Editor, The Racing Pigeon. London, W.C.1.
RENAL AUTOTRANSPLANTATION SIR,-Dr. Serrallach-Mila and his colleaguesmust surely be given the credit for first describing the treatment of renalartery stenosis by autotransplantation of the kidney to the iliac fossa. They were the first who actually did it, even if Mr. Dempster (Jan. 1) had suggested it before. This procedure seems to me a logical answer in certain cases where revascularisation of the kidney in its normal position is technically difficult. I have the impression that we shall be hearing more about this approach in the future. As Mr. Dempster points out, this form of autotransplantation of the kidney is also a solution to the problem of reestablishing ureteral continuity after injury or disease of a long segment of ureter. Hardy has reported a clinical case successfully treated by this method.2 The alternative of using intestine to bridge the gap may be more appealing to a greater number of surgeons with a different training, but this has the drawbacks of producing reflux, metabolic acidosis, and sometimes massive dilatation of the intestinal segment. General Hospital, Warrington, E. BENGOECHEA GONZALEZ. Lancashire.
ENZYMES IN DOWN’S SYNDROME SiR,-An increase of leucocyte alkaline phosphatase3 and
leucocyte glucose-6-phosphate dehydrogenase (G.-6-P.D.) 45 has been reported in patients with Down’s syndrome. We report here the activity of these two enzymes in the platelets of such patients. The platelets were prepared as described by Wurzel et al.B except that they were washed with 0-2% saline solution once to complete the destruction of erythrocytes, and lysis was carried out using saponin. G.-6-P.D. was assayed by the procedure of Kornberg and Horecker,’ and alkaline phosphatase by the method of Bessey et al.using p-nitrophenol phosphate as substrate at pH 9-3. There was no difference between the patients with Down’s syndrome and controls in G.-6-P.D. activity (expressed as platelet-count, or as protein content of nicotinamide-adenine dinucleotide phosphate [N.A.D.P.]) and alkaline-phosphatase activity, as follows (all values are expressed as mean standard error, and the numbers of subjects studied are given in parentheses):
quine-sensitive type of G.-6-P.D. deficiency, no abnormality in enzyme activity has been found in leucocytes 12 or fibroblasts 13 corresponding to the decrease seen in erythrocytes. Cox 14 reported that an extra chromosome 21 does not affect either the alkaline-phosphatase concentration or its mode of regulation in skin cultures derived from trisomic patients with Down’s syndrome. The failure to find an increase of either platelet alkaline phosphatase or platelet G.-6-P.D. in Down’s syndrome suggests that the increase in leucocyte alkaline phosphatase and leucocyte G.-6-P.D. probably represents not the direct action of a structural gene locus, but a more localised reaction. This would also provide further confirmation for the concept that platelets have a different origin from leucocytes and erythrocytes .15 We wish to thank Dr. N. Shahidi for his suggestions. These studies were supported by grants from the Illinois Mental Health Fund and the United States Public Health Service (TI-AM-5186). Children’s Memorial Hospital, and Department of Pediatrics, Northwestern University Medical School, Chicago.
LING-YU SHIH DAVID YI-YUNG HSIA.
NO CHARGE Sir,-I very surprised to read your annotation 16 about issued by general practitioners. prescriptions The implication of overprescribing by disillusioned doctors leaves a bitter taste in the mouth and must be far from the truth-except perhaps in some instances. At a time when critical negotiations are in progress to improve the National Health Service it is unwise to make damaging statements which could be detrimental to the profession. Let us face the facts-the public are conditioned to using free services, and, human nature being what it is, some people will quite naturally get all they can for nothing. This applies particularly to inadequate hypochondriacal personalities who constitute about 2% of every practice and are content to use their family doctor in the same way as they would a drug store. This 2% from each practice throughout the country, viewed collectively, represents a formidable destructive force within the N.H.S., and in the context of all the other social amenities and benefits which they astutely manoeuvre to their own advantage. This factor should be considered when planning future welfare schemes. GEORGE L. HINDSON. was
HELPING YOUR DOCTOR/PATIENT SIR,-It seems reasonable that, with so much recent publicity given to abuses of the National Health Service by patients, some efforts should be made to redress the balance. Two telephone calls from the daughter of a 66-year-old patient, a chronic and severe case of Parkinson’s disease, in the week before Christmas failed to produce a visit from the doctor. On Christmas Eve the patient fell, and a third phonecall finally brought the G.P. He left, leaving a Helping Your Doctor leaflet published by the Ministry of Health. Paragraphs 3 and 4 were marked, and the second half of the sentence in paragraph 3, pointing out that " Doctors are not under an obligation to see a patient just whenever and wherever the patient thinks fit ", was underlined. A final gesture was a note on the back of the leaflet: Please get your mother changed to another doctor." "
1.
2. 3. 4. 5. 6.
Serrallach-Mila, N., Paravisini, J., Mayol-Valls, P., Alberti, J., Casellas, A., Nolla-Panadés, J. Lancet, 1965, ii, 1130. Hardy, J. J. Am. med. Ass. 1963, 184, 97. Trubowitz, S., Kirman, D., Masek, B. Lancet, 1962, ii, 486. Mellman, W. J., Oski, F. A., Tedesco, T. A., Maciera-Coelho, A. Harris, H. ibid. 1964, ii, 674. Shih, L. Y., Wong, P., Inouye, T., Makler, M., Hsia, D. Y. Y. ibid. 1965, ii, 746. Wurzel, H., McCreary, T., Baker, L., Gumerman, L. Blood, 1961,
17, 314. Kornberg, A., Horecker, B. L. Meth. Enzym. 1955, 1, 323. Bessey, O. A., Lowry, O. H., Brock, M. J. J. biol. Chem. 1946, 164, 321. 9. Ramot, B., Fisher, S., Szeinberg, A., Adam, A., Chaim, S., Gafni, D. J. clin. Invest. 1959, 38, 2234. 10. Ramot, B., Szeinberg, A., Adam, A., Sheba, C., Gafni, D. ibid. p. 1659. 11. Gartler, S. M. Int. Congr. hum. Genet. 1961, 2, 622. 7. 8.
From this incident it appears that the Ministry have inadvertently provided general practitioners with a form, similar to that of a driving-test examiner, on which the appropriate
presumed faults in attitude of patients and their relatives
can
R. E. Nature, Lond. 1959,
183,
12. Marks,
P. A.,
Gross,
R.
T., Hurwitz,
1266.
Gartler, S. M. 4th Macy Conference on Genetics; p. 194. Ann Arbor, Michigan, 1964. 14. Cox, R. P. Expl Cell Res. 1965, 37, 690. 15. Saltzman, G. F. Acta med. scand. 1949, 132, suppl. 221. 16. Lancet, 1965, ii, 1172. 13.