- Email: [email protected]
IMMUNISATION AND THE COMPUTER
1366 ious
although it caused a substantial reduction of circulating lymphocytes. Further investigations of this case are in hand but in the meantime we feel that the use of anti-thymocyte serum in mycosis fungoides should be approached cautiously. T
Department of Dermatology, General Infirmary,
D. J. GOULD N. R. ROWELL
Leeds LSI 3EX
Department of Immunology,
H. ANTHONY
University of Leeds
RAPID DETECTION OF CHLORAMPHENICOL RESISTANCE IN HÆMOPHILUS INFLUENZÆ
SIR,—The emergence of &bgr;-lactamase-producing strains of Hœmophilus influenzœ type b emphasised the superiority of chloramphenicol over ampicillin for the treatment of hsemophilus meningitis and the other severe illnesses, mainly in children, caused by this organism. However, chloramphenicolresistant strains of H. influenzce type b have lately been reported in the U.S.A.’ and Britain.2 Such chloramphenicol resistance is enzyme dependent. Conventional sensivitity determination methods do not detect chloramphenicol-resistant strains of H. influenzce until at least 18 h after their primary isolation. Because speedy detection may be, literally, vital, we have devised a rapid method, easily carried out in any bacteriological laboratory, for detection of chloramphenicol inactivation. A plate of Oxoid Columbia agar is flooded with a barely turbid broth culture of chloramphenicol-sensitive Escherichia coli (N.C.T.C. strain 10418). After drying to remove surface fluid from the plate, discs of Whatman no. 1 filterpaper, 8.5 mm in diameter are placed on it. A wire loop is used to scrape off growth from the surface of the H. influenzœ culture to be tested. A heavy inoculum of the organism is applied evenly over the surface of one of the discs. Two other discs are similarly inoculated with a stock strain of H. influenzce that is chloramphenicol sensitive. After a delay of about 5 min, 10 µg/ml chloramphenicol discs (Oxoid), 7 mm in diameter, are carefully placed centrally on the disc inoculated with the test 1. Centre for Disease Control Morbid. Mortal. wkly Rep. 1976, 2. Kinmonth, A. L., Storrs, C. N., Mitchell, R. G. Br. med. J.
25, 386. (in the press).
organism and on one of the discs inoculated with the control organism. If a chloramphenicol-resistant strain is available this would be used as another control. The chloramphenicol thus has to pass through the larger disc to reach the culture medium; it will fail to do so in an active state if the larger disc has been inoculated with a strain that is producing chloramphenicol acetyltransferase. 210 min incubation of the plate at 40 °C results in visible growth of the E. coli, with a zone of inhibition around the disc inoculated with the chloramphenicolsensitive strain. The zone of inhibition is much reduced or absent around a chloramphenicol disc that has been placed on a larger disc inoculated with a strain that is inactivating chlor-
amphenicol (see figure). Chloramphenicol-resistant
strains of H. influenzœ are still and we have been able to test only three of them. We found the minimum inhibitory concentration of chloramphenicol for each of these to be 16 µg/ml; all three gave convincing evidence of chloramphenicol destruction when tested as described above, provided that the cultures used were not more than 24 h old. We are exploring the application of modifications of this method to the rapid detection of other types of enzyme-dependent antibiotic resistance. rare
Department of Bacteriology and Regional Public Health Laboratory, Radcliffe Infirmary, Oxford OX2 6HE
MARY P. E. SLACK D. B. WHELDON D. C. TURK
IMMUNISATION AND THE COMPUTER
SIR,-Following the suggestion by Dr Bussey and Mr Holmes (Nov. 5, p. 970) that computer management of immunisation schedules in West Sussex had maintained high immunisation-rates in face of a national decline, Dr Adams of Rotherham A.H.A. (Nov. 19, p. 1079) countered by contrasting falling rates among children in the part of her area with a computer-assisted scheme with rising rates in another part where a different immunisation schedule was managed manually. The computing system used in the part of Rotherham A.H.A. concerned is operated by the Trent R.H.A.’S computer, which also services parts of three other areas of south Yorkshire. Examination of the trends in immunisation-rates in these areas among children whose schedules are arranged by computer confirms that the Rotherham rates are falling but shows that rates in the other three areas are either remaining steady or increasing. Moreover the latest Rotherham rates for each disease are lower than those of other areas. IMMUNISATION-RATES*
SOUTH YORKSHIRE COMPUTER-ASSISTED
SCHEME,
BY YEAR OF BIRTH
*No. children born in a particular year who had completed primary of immunisation 27months after Jan. 1 of year concerned. tFigures for tetanus the same, except 64% for Doncaster in 1975. Rotherham rates utilise more complete data than those supplied by Dr Adams.
course
Growth of E. coli.
(A) Chloramphenicol-inactivating strain of H. influenzce type b. (B) Chloramphenicol-sensitive strain. (C) Control sensitive strain (no chloramphenicol disc applied).
1’he ’plate was incubated for 3 h at 40 °C.
For the most part these data support the West Sussex contention that computer assistance prevents a decline in immunisation-rates. However, the generally low levels of uptake shown here are in line with those reported by Dr Farries (Dec. 3, p. 1184) for Bolton and suggest that there are more critical
1367 factors than computer assistance involved in rates of coverage. Trent
Regional Health Authority, B. T. WILLIAMS
Sheffield S10 3TH
ŒSTROGENS AND EXTRAPYRAMIDAL SYSTEM
promoting high
METABOLIC RESPONSE TO FOOD
SIR,—We have measured changes in resting metabolic rate after food ingestion in 15 subjects of various weights. 2 men, 10 women, and 3 male adolescents were studied. Heat loss (radiant, convective, conductive, and evaporative), which reflects the resting metabolic rate,1-3 was measured using gradient-layer calorimetry. The subjects fasted for 8 h and heat losses were then measured for 1 h. Each subject then consumed a milkshake equivalent to 1593 kj (381 calories, carbohydrate, protein, and fats providing 50, 12, and 38% respectively). After 20 min, heat loss was again determined for 1 h. The % change in metablic rate was plotted against the subjects’ bodyweight expressed as % ideal body-weight (see figure), and an association was found (r=-0.38, P=0.12). There was thus a tendency for the metabolic rate to rise in thin subjects but fall in
SIR,-Brain amines can affect pituitary hormone secretion, especially prolactin secretion, dopamine seeming to be the main or even the only substance of hypothalamic origin which inhibits prolactin secretion.’ The reverse may also be true; hormones can affect chemical synaptic transmission in the central nervous system.1-3 This is illustrated by the observation that oestrogen administration to patients receiving neuroleptics seemed to facilitate the appearance of parkinsonian symp-
toms.4 Current theories on the functioning of the extrapyramidal system suggest a balance between dopaminergic and cholinergic influences. While tardive dyskinesia is usually observed after long-term neuroleptics, agents decreasing dopaminergic activity have some beneficial effect on tardive dyskinesia, pointing to a critical role for dopamine receptors in the pathogenesis of this neurological side-effect5-10 When used to treat Parkinson’s disease levodopa can induce similar dyskinesias which can also be controlled by antidopaminergic drugs such as
neuroleptics.ll.12 Tardive dyskinesia has been reported to be
more frequent in elderly females, though a clear relationship between tardive dyskinesia and female sex is inconclusive.9 Nevertheless, since the production of female sex hormones decreases with age, oestrogens could play some protective role against the development of this neurological complication. This possibility is supported by the findings that 17&bgr;-œstradiol can almost completely reverse the inhibitory effect of two dopamine agonists on both basal and thyrotropin-releasing hormone (T.R.H.)induced prolactin release. 13 We have seen two female patients in whom symptoms of levodopa-induced dyskinesia and neuroleptic-induced tardive buccolinguomasticatory dyskinesia could have been markedly influenced by circulating levels of oestrogens.
Case1 This
64-year-old
woman
had her menopause
at
the age of
1.
Association between % ideal body-weight and changes in metabolic rate produced by food consumption.
resting
8=males; O=females. Patient A had a phaeochromocytoma. obese subjects. This suggests that the thermogenic response to food may contribute to refractory weight control in obese and thin people. Our results agree with those of Green and Miller’ who studied responses to food in persons of varied % ideal body-weight by monitoring oxygen consumption. These findings support clinical evidence that weight can be maintained on a wide range of energy intakes5,6 and that metabolic rate may be depressed in obese patients.7
Labrie, F., Beaulieu, M., Caron, M., Raymond, V. in Proceedings of International Symposium in Prolactin (edited by C. Robyn and M. Harter). Amsterdam (in the press). 2. Hackman, E., Wirz-Justice, A., Lichtsteiner, M. Psychopharmacologia, 1973, 32, 183. 3. Jori, A., Dolfini, E. Neuroendocrinology, 1976, 21, 74. 4. Gratton, L. Union med. Can. 1960, 89, 679. 5. Villeneuve, A., Böszörményi, Z. Lancet, 1970, 1, 353. 6. Villeneuve, A., Böszörményi, Z., Deschambault, M., Lachance, R., Laval med. 1970 41, 923. 7. Tarsy, D., Baldessarini, R. J. in Clinical Neuropharmacology (edited by H. L. Klawans); vol. I, p. 29. New York, 1976. 8. Marsden, C. D., Tarsy, D., Baldessarini, R. J. in Psychiatric Aspects of Neurologic Disease (edited by D. F. Benson, and D. Blumer); p. 219. New York, 1975. 9. Baldessarini, R. J., Tarsy, D. Paper presented at meeting of the American College of Neuropsychopharmacology, held in New Orleans, in 1976. 10. Villeneuve, A. in Neuro-Psychopharmacology (edited by P. Deniker, C. Radouco-Thomas, and A. Villeneuve); p. 709. Oxford (in the press). 11. Klawans, H. J., Weiner, W. J. J. Neurol. Neurosurg. 1974, 37, 427. 12. Tarsy, D., Parkes, J. D. and Marsden, C. D. ibid. 1975, 38, 331. 13. Raymond, V., Beaulieu, M., Labrie, F., Boissier, J. R. Unpublished.
We thank Ms Linda Westbury for monitoring and measuring the subjects and the medical staff of the Family Practice Center for patient
referral.
Departments of Medicine Family Practice;
and
General Clinical Research Center; and Department of Surgery, Medical University of South Carolina Charleston, South Carolina 29401, U.S.A.
R. K. ROBSON MARY JOAN OEXMAN MARGARET S. COALE GILBERT B. BRADHAM
J.
1. Bradham, G. B. J. S. Carol. med. Ass., 1975, 71, 357. 2. Bradham, G. B. J. Am. med. Ass. 1966, 198. 746. 3. Bradham, G. B. Sth. med. J., Nashville, 1974, 67, 967. 4. Green, E., Miller, D. S. Proc. Nutr. Soc. 1975, 34, 14a. 5. Rose, G. A., Williams, R. T. Br. J. Nutr. 1961 15, 1 6. Gulick, A. Am J. Physiol. 1922, 60, 371. 7. Miller, D. S., Parsonage, S. Lancet, 1975, i, 773.
Dyskinesia scores in patient premarin per day.
with
(+)
or
without
(-) 0.625
mg
although it caused a substantial reduction of circulating lymphocytes. Further investigations of this case are in hand but in the meantime we feel that the use of anti-thymocyte serum in mycosis fungoides should be approached cautiously. T
Department of Dermatology, General Infirmary,
D. J. GOULD N. R. ROWELL
Leeds LSI 3EX
Department of Immunology,
H. ANTHONY
University of Leeds
RAPID DETECTION OF CHLORAMPHENICOL RESISTANCE IN HÆMOPHILUS INFLUENZÆ
SIR,—The emergence of &bgr;-lactamase-producing strains of Hœmophilus influenzœ type b emphasised the superiority of chloramphenicol over ampicillin for the treatment of hsemophilus meningitis and the other severe illnesses, mainly in children, caused by this organism. However, chloramphenicolresistant strains of H. influenzce type b have lately been reported in the U.S.A.’ and Britain.2 Such chloramphenicol resistance is enzyme dependent. Conventional sensivitity determination methods do not detect chloramphenicol-resistant strains of H. influenzce until at least 18 h after their primary isolation. Because speedy detection may be, literally, vital, we have devised a rapid method, easily carried out in any bacteriological laboratory, for detection of chloramphenicol inactivation. A plate of Oxoid Columbia agar is flooded with a barely turbid broth culture of chloramphenicol-sensitive Escherichia coli (N.C.T.C. strain 10418). After drying to remove surface fluid from the plate, discs of Whatman no. 1 filterpaper, 8.5 mm in diameter are placed on it. A wire loop is used to scrape off growth from the surface of the H. influenzœ culture to be tested. A heavy inoculum of the organism is applied evenly over the surface of one of the discs. Two other discs are similarly inoculated with a stock strain of H. influenzce that is chloramphenicol sensitive. After a delay of about 5 min, 10 µg/ml chloramphenicol discs (Oxoid), 7 mm in diameter, are carefully placed centrally on the disc inoculated with the test 1. Centre for Disease Control Morbid. Mortal. wkly Rep. 1976, 2. Kinmonth, A. L., Storrs, C. N., Mitchell, R. G. Br. med. J.
25, 386. (in the press).
organism and on one of the discs inoculated with the control organism. If a chloramphenicol-resistant strain is available this would be used as another control. The chloramphenicol thus has to pass through the larger disc to reach the culture medium; it will fail to do so in an active state if the larger disc has been inoculated with a strain that is producing chloramphenicol acetyltransferase. 210 min incubation of the plate at 40 °C results in visible growth of the E. coli, with a zone of inhibition around the disc inoculated with the chloramphenicolsensitive strain. The zone of inhibition is much reduced or absent around a chloramphenicol disc that has been placed on a larger disc inoculated with a strain that is inactivating chlor-
amphenicol (see figure). Chloramphenicol-resistant
strains of H. influenzœ are still and we have been able to test only three of them. We found the minimum inhibitory concentration of chloramphenicol for each of these to be 16 µg/ml; all three gave convincing evidence of chloramphenicol destruction when tested as described above, provided that the cultures used were not more than 24 h old. We are exploring the application of modifications of this method to the rapid detection of other types of enzyme-dependent antibiotic resistance. rare
Department of Bacteriology and Regional Public Health Laboratory, Radcliffe Infirmary, Oxford OX2 6HE
MARY P. E. SLACK D. B. WHELDON D. C. TURK
IMMUNISATION AND THE COMPUTER
SIR,-Following the suggestion by Dr Bussey and Mr Holmes (Nov. 5, p. 970) that computer management of immunisation schedules in West Sussex had maintained high immunisation-rates in face of a national decline, Dr Adams of Rotherham A.H.A. (Nov. 19, p. 1079) countered by contrasting falling rates among children in the part of her area with a computer-assisted scheme with rising rates in another part where a different immunisation schedule was managed manually. The computing system used in the part of Rotherham A.H.A. concerned is operated by the Trent R.H.A.’S computer, which also services parts of three other areas of south Yorkshire. Examination of the trends in immunisation-rates in these areas among children whose schedules are arranged by computer confirms that the Rotherham rates are falling but shows that rates in the other three areas are either remaining steady or increasing. Moreover the latest Rotherham rates for each disease are lower than those of other areas. IMMUNISATION-RATES*
SOUTH YORKSHIRE COMPUTER-ASSISTED
SCHEME,
BY YEAR OF BIRTH
*No. children born in a particular year who had completed primary of immunisation 27months after Jan. 1 of year concerned. tFigures for tetanus the same, except 64% for Doncaster in 1975. Rotherham rates utilise more complete data than those supplied by Dr Adams.
course
Growth of E. coli.
(A) Chloramphenicol-inactivating strain of H. influenzce type b. (B) Chloramphenicol-sensitive strain. (C) Control sensitive strain (no chloramphenicol disc applied).
1’he ’plate was incubated for 3 h at 40 °C.
For the most part these data support the West Sussex contention that computer assistance prevents a decline in immunisation-rates. However, the generally low levels of uptake shown here are in line with those reported by Dr Farries (Dec. 3, p. 1184) for Bolton and suggest that there are more critical
1367 factors than computer assistance involved in rates of coverage. Trent
Regional Health Authority, B. T. WILLIAMS
Sheffield S10 3TH
ŒSTROGENS AND EXTRAPYRAMIDAL SYSTEM
promoting high
METABOLIC RESPONSE TO FOOD
SIR,—We have measured changes in resting metabolic rate after food ingestion in 15 subjects of various weights. 2 men, 10 women, and 3 male adolescents were studied. Heat loss (radiant, convective, conductive, and evaporative), which reflects the resting metabolic rate,1-3 was measured using gradient-layer calorimetry. The subjects fasted for 8 h and heat losses were then measured for 1 h. Each subject then consumed a milkshake equivalent to 1593 kj (381 calories, carbohydrate, protein, and fats providing 50, 12, and 38% respectively). After 20 min, heat loss was again determined for 1 h. The % change in metablic rate was plotted against the subjects’ bodyweight expressed as % ideal body-weight (see figure), and an association was found (r=-0.38, P=0.12). There was thus a tendency for the metabolic rate to rise in thin subjects but fall in
SIR,-Brain amines can affect pituitary hormone secretion, especially prolactin secretion, dopamine seeming to be the main or even the only substance of hypothalamic origin which inhibits prolactin secretion.’ The reverse may also be true; hormones can affect chemical synaptic transmission in the central nervous system.1-3 This is illustrated by the observation that oestrogen administration to patients receiving neuroleptics seemed to facilitate the appearance of parkinsonian symp-
toms.4 Current theories on the functioning of the extrapyramidal system suggest a balance between dopaminergic and cholinergic influences. While tardive dyskinesia is usually observed after long-term neuroleptics, agents decreasing dopaminergic activity have some beneficial effect on tardive dyskinesia, pointing to a critical role for dopamine receptors in the pathogenesis of this neurological side-effect5-10 When used to treat Parkinson’s disease levodopa can induce similar dyskinesias which can also be controlled by antidopaminergic drugs such as
neuroleptics.ll.12 Tardive dyskinesia has been reported to be
more frequent in elderly females, though a clear relationship between tardive dyskinesia and female sex is inconclusive.9 Nevertheless, since the production of female sex hormones decreases with age, oestrogens could play some protective role against the development of this neurological complication. This possibility is supported by the findings that 17&bgr;-œstradiol can almost completely reverse the inhibitory effect of two dopamine agonists on both basal and thyrotropin-releasing hormone (T.R.H.)induced prolactin release. 13 We have seen two female patients in whom symptoms of levodopa-induced dyskinesia and neuroleptic-induced tardive buccolinguomasticatory dyskinesia could have been markedly influenced by circulating levels of oestrogens.
Case1 This
64-year-old
woman
had her menopause
at
the age of
1.
Association between % ideal body-weight and changes in metabolic rate produced by food consumption.
resting
8=males; O=females. Patient A had a phaeochromocytoma. obese subjects. This suggests that the thermogenic response to food may contribute to refractory weight control in obese and thin people. Our results agree with those of Green and Miller’ who studied responses to food in persons of varied % ideal body-weight by monitoring oxygen consumption. These findings support clinical evidence that weight can be maintained on a wide range of energy intakes5,6 and that metabolic rate may be depressed in obese patients.7
Labrie, F., Beaulieu, M., Caron, M., Raymond, V. in Proceedings of International Symposium in Prolactin (edited by C. Robyn and M. Harter). Amsterdam (in the press). 2. Hackman, E., Wirz-Justice, A., Lichtsteiner, M. Psychopharmacologia, 1973, 32, 183. 3. Jori, A., Dolfini, E. Neuroendocrinology, 1976, 21, 74. 4. Gratton, L. Union med. Can. 1960, 89, 679. 5. Villeneuve, A., Böszörményi, Z. Lancet, 1970, 1, 353. 6. Villeneuve, A., Böszörményi, Z., Deschambault, M., Lachance, R., Laval med. 1970 41, 923. 7. Tarsy, D., Baldessarini, R. J. in Clinical Neuropharmacology (edited by H. L. Klawans); vol. I, p. 29. New York, 1976. 8. Marsden, C. D., Tarsy, D., Baldessarini, R. J. in Psychiatric Aspects of Neurologic Disease (edited by D. F. Benson, and D. Blumer); p. 219. New York, 1975. 9. Baldessarini, R. J., Tarsy, D. Paper presented at meeting of the American College of Neuropsychopharmacology, held in New Orleans, in 1976. 10. Villeneuve, A. in Neuro-Psychopharmacology (edited by P. Deniker, C. Radouco-Thomas, and A. Villeneuve); p. 709. Oxford (in the press). 11. Klawans, H. J., Weiner, W. J. J. Neurol. Neurosurg. 1974, 37, 427. 12. Tarsy, D., Parkes, J. D. and Marsden, C. D. ibid. 1975, 38, 331. 13. Raymond, V., Beaulieu, M., Labrie, F., Boissier, J. R. Unpublished.
We thank Ms Linda Westbury for monitoring and measuring the subjects and the medical staff of the Family Practice Center for patient
referral.
Departments of Medicine Family Practice;
and
General Clinical Research Center; and Department of Surgery, Medical University of South Carolina Charleston, South Carolina 29401, U.S.A.
R. K. ROBSON MARY JOAN OEXMAN MARGARET S. COALE GILBERT B. BRADHAM
J.
1. Bradham, G. B. J. S. Carol. med. Ass., 1975, 71, 357. 2. Bradham, G. B. J. Am. med. Ass. 1966, 198. 746. 3. Bradham, G. B. Sth. med. J., Nashville, 1974, 67, 967. 4. Green, E., Miller, D. S. Proc. Nutr. Soc. 1975, 34, 14a. 5. Rose, G. A., Williams, R. T. Br. J. Nutr. 1961 15, 1 6. Gulick, A. Am J. Physiol. 1922, 60, 371. 7. Miller, D. S., Parsonage, S. Lancet, 1975, i, 773.
Dyskinesia scores in patient premarin per day.
with
(+)
or
without
(-) 0.625
mg