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VASOMOTOR-REFLEX RESPONSE IN MIGRAINE
152 NUMBERS
AND GRADES OF ANALYSABLE METAPHASE FIGURES EXPOSURE OF LEUCOCYTE CULTURES TO COLCHICINE
be lessened
AFTER
Dr. Appenzeller may label a study such as ours or that of Dr. Hockaday and her colleagues as a " negative investigation ", but the fundamental fact remains that his findings have In view of this we feel not been confirmed by other workers. that at present there is inadequate evidence to support Dr. is only one facet of a Appenzeller’s contention that migraine generalised vasomotor disorder.5 Royal Infirmary and B. W. LASSERS Western General Hospital, E. B. FRENCH. Edinburgh.
the morphological changes result from long exposure to colchicine. This modification has been found to be of value when the amount of sample to be processed must be restricted in order to conserve time, as in surveys of large numbers of normal people. This method is now used routinely in a survey of normal newborns, in which one technician processes and analyses up to one hundred specimens each month. A minor modification of the microtechnique for peripheralblood culture was used.’ Blood-samples consisted of three drops of heel-prick blood from normal newborn infants, and were processed in two parallel groups, which differed in the concentration of colchicine and in the time of exposure to this agent. In one group of 20 cultures, colchicine was added to a final concentration of 0.005 fLg. per ml. after about 56 hours and the cultures were incubated at 37°C for a further 16 hours. In a second set of 20 cultures, colchicine was added to a final concentration of 0.04 g. per ml. after about 72 hours and the cultures were incubated for only 2 additional hours (the routine procedure previously used in this laboratory). All cultures were treated by a modification of the method of Moorhead et awl. Two different observers independently counted and graded the analysable metaphase figures, scanning exactly the same regions of each slide for every specimen (see accompanying table). Each analysable figure was graded as good, fair, or poor, and the percentages of these grades were roughly the same in the two groups. However, there was a striking increase in the total number of analysable mitoses with longer exposure to colchicine, thus significantly increasing the absolute number available for analysis and decreasing the number of slides that need to be examined.
not seem to
despite
(contractions and breaks) known
to
INFECTION IN RHEUMATOID ARTHRITIS
SIR,-Your annotation6 discusses Walker’s finding of an increased incidence of pneumonia, bronchitis, and bronchiectasis in male patients with rheumatoid arthritis before the of the disease.7 In the course of a study of fertility in 230 women with rheumatoid arthritis and 230 non-rheumatoid female controls matched for age and social statusahistory of chest infection was noted more often in rheumatoid patients than in controls. This finding can be summarised as follows:
onset
Of the 43 rheumatoid patients who gave a history of bronchitis or bronchiectasis, this had preceded the onset of rheumatoid arthritis in 28. Similarly, of the 20 rheumatoid patients who gave a history of pneumonia or pleurisy, 17 stated that this had preceded the onset of the disease. Department of Rheumatology, St. Mary Abbots Hospital, London W.8.
APRIL KAY.
MUCOPOLYSACCHARIDES IN HURLER’S SYNDROME SIR,-The article by Dr. Danes and Professor Bearn (May 13, p. 1029) prompts me to refer to my own work. Since it is known that vitamin A in high dosage disrupts lysosomes in vitro These studies were supported in part by grants from the Children’s and apparently in vivo, it was decided to treat 5 cases of mucoBureau (H-89) and the John A. Hartford Foundation. polysaccharide defects with high doses (50,000-100,000 units Clinical Genetics Division, per day) of vitamin A. Each of these subjects had had more Children’s Hospital Medical Center, GERMAINE BREAU than a hundred 24-hour urine assays before therapy and each and Department of Pediatrics, S. WALZER was maintained on therapy for a minimum of 6 months. The Harvard Medical School, P. S. GERALD. Boston, Massachusetts 02115, U.S.A. acid-mucopolysaccharide excretion varies considerably from day to day in these patients normally; in none was any change noted in the average daily excretion of mucopolysaccharides; nor was there any change in the various constituents of each RESPONSE IN MIGRAINE VASOMOTOR-REFLEX SiR,—In your correspondence columns of July 1 Dr. acid mucopolysaccharide. Since it had been shown previously that steroids will inhibit Hockaday and her colleagues (p. 49) and Dr. Appenzeller the incorporation of labelled sulphate into acid mucopolyat their views diametrically opposed length (p. 48) express regarding vasomotor-reflex response in migrainous subjects. saccharides produced within the liver, it was decided to try high dosages of steroid therapy (cortisone acetate) in one of our Our results3 support Dr. Hockaday and her colleagues, finding more severely affected patients. There was no change in the that there is no significant difference between migraine and excretion pattern, although the child did seem to improve in in the hand in reflex vasodilatation non-migraine subjects somewhat clinically. He suddenly developed pneumonia and 4 response to radiant heating of the trunk. We studied 15 within a short time. There was no change in sulphate/ migrainous subjects and 11 migraine-free controls and found died uronic-acid or sulphate/hexosamine ratios. His liver had an that both groups behaved identically. In addition we do not acid-mucopolysaccharide content of about 0’1%, which was think that Dr. Appenzeller’s results can be attributed to the much lower than that (3%) found in a similar patient who had administration of ergotamine. Two of our subjects had taken been treated with steroids; it seemed to contain very high ergotamine within 24 hours of being studied and both behaved not amounts of lipid, and I am investigating this at present. studied before and after the one subject normally. Moreover, The ketogenic diet and pimetine hydrochloride (IN379) oral administration of ergotamine showed a normal vasohave also been given prolonged clinical trials without ascertaindilator response to heating although the absolute volumes of able biochemical or clinical results. were reduced. flow Arakaki, D. T., Sparkes, R. S. Cytogenetics, 1963, 2, 57. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., Hungerford, D. A. Expl Cell Res. 1960, 20, 613. 3. French, E. B., Lassers, B. W., Desai, M. G. J. Neurol. Neurosurg. Psychiat. 1967, 30, 276. 4. Hockaday, J. M., Macmillan, A. L., Whitty, C. W. M. Lancet, 1967, i, 1023.
1. 2.
Murdoch Center,
Butner, North Carolina 27509.
A. W. RENUART.
Appenzeller, O., Davison, K., Marshall, J. J. Neurol. Neurosurg. Psychiat. 1963, 26, 447. 6. Lancet, 1967, i, 1372. 7. Walker, W. C. Q. Jl Med. 1967, 36, 239. 8. Kay, A., Bach, F. Ann. rheum. Dis. 1965, 24, 169.
5.
AND GRADES OF ANALYSABLE METAPHASE FIGURES EXPOSURE OF LEUCOCYTE CULTURES TO COLCHICINE
be lessened
AFTER
Dr. Appenzeller may label a study such as ours or that of Dr. Hockaday and her colleagues as a " negative investigation ", but the fundamental fact remains that his findings have In view of this we feel not been confirmed by other workers. that at present there is inadequate evidence to support Dr. is only one facet of a Appenzeller’s contention that migraine generalised vasomotor disorder.5 Royal Infirmary and B. W. LASSERS Western General Hospital, E. B. FRENCH. Edinburgh.
the morphological changes result from long exposure to colchicine. This modification has been found to be of value when the amount of sample to be processed must be restricted in order to conserve time, as in surveys of large numbers of normal people. This method is now used routinely in a survey of normal newborns, in which one technician processes and analyses up to one hundred specimens each month. A minor modification of the microtechnique for peripheralblood culture was used.’ Blood-samples consisted of three drops of heel-prick blood from normal newborn infants, and were processed in two parallel groups, which differed in the concentration of colchicine and in the time of exposure to this agent. In one group of 20 cultures, colchicine was added to a final concentration of 0.005 fLg. per ml. after about 56 hours and the cultures were incubated at 37°C for a further 16 hours. In a second set of 20 cultures, colchicine was added to a final concentration of 0.04 g. per ml. after about 72 hours and the cultures were incubated for only 2 additional hours (the routine procedure previously used in this laboratory). All cultures were treated by a modification of the method of Moorhead et awl. Two different observers independently counted and graded the analysable metaphase figures, scanning exactly the same regions of each slide for every specimen (see accompanying table). Each analysable figure was graded as good, fair, or poor, and the percentages of these grades were roughly the same in the two groups. However, there was a striking increase in the total number of analysable mitoses with longer exposure to colchicine, thus significantly increasing the absolute number available for analysis and decreasing the number of slides that need to be examined.
not seem to
despite
(contractions and breaks) known
to
INFECTION IN RHEUMATOID ARTHRITIS
SIR,-Your annotation6 discusses Walker’s finding of an increased incidence of pneumonia, bronchitis, and bronchiectasis in male patients with rheumatoid arthritis before the of the disease.7 In the course of a study of fertility in 230 women with rheumatoid arthritis and 230 non-rheumatoid female controls matched for age and social statusahistory of chest infection was noted more often in rheumatoid patients than in controls. This finding can be summarised as follows:
onset
Of the 43 rheumatoid patients who gave a history of bronchitis or bronchiectasis, this had preceded the onset of rheumatoid arthritis in 28. Similarly, of the 20 rheumatoid patients who gave a history of pneumonia or pleurisy, 17 stated that this had preceded the onset of the disease. Department of Rheumatology, St. Mary Abbots Hospital, London W.8.
APRIL KAY.
MUCOPOLYSACCHARIDES IN HURLER’S SYNDROME SIR,-The article by Dr. Danes and Professor Bearn (May 13, p. 1029) prompts me to refer to my own work. Since it is known that vitamin A in high dosage disrupts lysosomes in vitro These studies were supported in part by grants from the Children’s and apparently in vivo, it was decided to treat 5 cases of mucoBureau (H-89) and the John A. Hartford Foundation. polysaccharide defects with high doses (50,000-100,000 units Clinical Genetics Division, per day) of vitamin A. Each of these subjects had had more Children’s Hospital Medical Center, GERMAINE BREAU than a hundred 24-hour urine assays before therapy and each and Department of Pediatrics, S. WALZER was maintained on therapy for a minimum of 6 months. The Harvard Medical School, P. S. GERALD. Boston, Massachusetts 02115, U.S.A. acid-mucopolysaccharide excretion varies considerably from day to day in these patients normally; in none was any change noted in the average daily excretion of mucopolysaccharides; nor was there any change in the various constituents of each RESPONSE IN MIGRAINE VASOMOTOR-REFLEX SiR,—In your correspondence columns of July 1 Dr. acid mucopolysaccharide. Since it had been shown previously that steroids will inhibit Hockaday and her colleagues (p. 49) and Dr. Appenzeller the incorporation of labelled sulphate into acid mucopolyat their views diametrically opposed length (p. 48) express regarding vasomotor-reflex response in migrainous subjects. saccharides produced within the liver, it was decided to try high dosages of steroid therapy (cortisone acetate) in one of our Our results3 support Dr. Hockaday and her colleagues, finding more severely affected patients. There was no change in the that there is no significant difference between migraine and excretion pattern, although the child did seem to improve in in the hand in reflex vasodilatation non-migraine subjects somewhat clinically. He suddenly developed pneumonia and 4 response to radiant heating of the trunk. We studied 15 within a short time. There was no change in sulphate/ migrainous subjects and 11 migraine-free controls and found died uronic-acid or sulphate/hexosamine ratios. His liver had an that both groups behaved identically. In addition we do not acid-mucopolysaccharide content of about 0’1%, which was think that Dr. Appenzeller’s results can be attributed to the much lower than that (3%) found in a similar patient who had administration of ergotamine. Two of our subjects had taken been treated with steroids; it seemed to contain very high ergotamine within 24 hours of being studied and both behaved not amounts of lipid, and I am investigating this at present. studied before and after the one subject normally. Moreover, The ketogenic diet and pimetine hydrochloride (IN379) oral administration of ergotamine showed a normal vasohave also been given prolonged clinical trials without ascertaindilator response to heating although the absolute volumes of able biochemical or clinical results. were reduced. flow Arakaki, D. T., Sparkes, R. S. Cytogenetics, 1963, 2, 57. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M., Hungerford, D. A. Expl Cell Res. 1960, 20, 613. 3. French, E. B., Lassers, B. W., Desai, M. G. J. Neurol. Neurosurg. Psychiat. 1967, 30, 276. 4. Hockaday, J. M., Macmillan, A. L., Whitty, C. W. M. Lancet, 1967, i, 1023.
1. 2.
Murdoch Center,
Butner, North Carolina 27509.
A. W. RENUART.
Appenzeller, O., Davison, K., Marshall, J. J. Neurol. Neurosurg. Psychiat. 1963, 26, 447. 6. Lancet, 1967, i, 1372. 7. Walker, W. C. Q. Jl Med. 1967, 36, 239. 8. Kay, A., Bach, F. Ann. rheum. Dis. 1965, 24, 169.
5.