739
plastic cannula of a 20-gauge ’Abbocath-T’ intravenous needle to connect the giving set to the fine-bore tubing. This cannula is less likely to perforate the tubing wall at the point of contact if flexion occurs there. As Mr Crow points out (Sept. 23, p. 690) a set comprising guide-wire and fine bore tubing with an attached Luer connection is now commercially available. Patient acceptability has been good, and one man has been inserting his own tube when necessary. An important point in the acceptability of these fine tubes seems to be their ability to allow normal deglutition of ordinary food. We have not found a.constant-rate infusion pump necessary; the limitation of flow-rate provided by the fine diameter of the tubing, as pointed out by Metz et al., is an important factor in the prevention of complications. Severe diarrhoea or gastric stasis can often be overcome by decreasing the dilution of the feeding solutions over a period of 8-10 days. During this time supplementation may be necessary. parenteral This method of feeding is cheaper and safer than parenteral nutrition. Our experience and that of Metz et al. suggests that it should be considered in all patients with an intact gastrointestinal tract who require nutritional supplementation. Department of Surgery, Royal Victoria Infirmary, Newcastle upon Tyne NE 1
A. J. RICH M. E. WHITEHOUSE P. D. WRIGHT
4LI
CONGENITAL INSENSITIVITY TO PAIN AND NALOXONE
Yanagida (Sept. 2, p. 520) is conattempt explain the syndrome of congenital insensitivity to pain by invoking a permanent hyperactivity of an endogenous morphine-like system. However, the naloxone injections should have been done double-blind with placebo control. Moreover, the doses of naloxone (2 and 10 mg) were SIR,-The report from
sistent with
our
Dr
to
large, and we need to know if such doses affect tooth pulp evoked potentials of normal subjects. We used 0.8 mg and sometimes 1.2mg naloxone2after checking that there was no significant effect (on the threshold of the nociceptive flexion reflex of a flexor muscle of the lower limb3) in normal subjects. Our two patients had a classical congenital insensitivity to pain:4 they had lacked pain sensation from birth, the entire body was affected, and all other sensations, particularly thermal sensations, were perceived normally. They could discriminate accurately between hot and cold. Neuropathological examinations failed to reveal any abnormality in the peripheral and central nervous systems.4 In contrast Yanagida’s patient failed to perceive thermal sensations (hot and cold) and had had numerous skeletal fractures resulting in "multiple joint deformities of the Charcot type", as in the cases described by Swansons and by Chatrian et al. This syndrome is called "congenital insensitivity to pain with anhydrosis". In these cases the neuropathologist finds absence of small neurons in the dorsal-root ganglia, lack of small fibres in the dorsal roots, absence of Lissauer tract at all levels in the spinal cord, and reduction in size of the descending tract of the trigeminal nerve in the medulla and cord, with great decrease of small fibres of this tract. "These histologic findings suggest that these patients’ defects in pain and temperature were related to absence, probably due to defective development of small primary sensory neurons, classically believed to subserve these sensations".6 Histologically, therefore, congenital insensitivity to pain and congenital insensitivity to pain with anhydrosis 1. Dehen, H., Willer, J. C., Boureau, F., Cambier, J. Lancet, 1977, ii, 293. 2. Dehen, H., Willer, J C., Cambier, J. Paper presented at the 2nd World Congress on Pain, held m Montreal, in August, 1978. 3. Boureau, F., Willer,J.C., Dauther, C. J. Neuropharmac. 1978, 17, 565. 4. Thrush, D.C. Brain, 1973, 96, 369. 5. Swanson, A. G. ArchsNeurol. 1963, 8, 299. 6. Chatrian, G. E., Farrell, D. F., Canfield, R. C., Reegt, E. L. ibid. 1975, 32, 141 7. Swanson, A. G., Buchan, G. C., Alvord, E. C. ibid. 1965, 12, 12.
Nevertheless, if naloxone does enhance nocievoked potentials in cases such as Yanagida’s this would prompt questions about the relations between the endogenous opiates and the small afferent fibres and the small priare
very different.
ceptive
mary sensory
neurons.
Laboratory of Clinical Neurophysiology, Hôpital Saint-Antoine, 75012 Paris, France; and Department of Clinical Neurology,
Hôpital Beaujon, Clichy
J. C. WILLER H. DEHEN F. BOUREAU J. CAMBIER
ELEVATED METABOLIC RATES IN OBESITY
SIR,-Dr James and his colleagues (Aug. 26, p. 472) confirm the decrease in resting metabolic rate (R.M.R.) upon slimming and comment on the discrepancy between the observed decrease in R.M.R. and that expected from changes in metabolic size. In their original article! they suggest that "energy-dissipating mechanisms appear to be involved". I and my colleagues have studied the thermal responses of five obese females undergoing weight reduction.2 The women were studied in a thermoneutral environment before and during a dietary intake of approximately 4-2 MJ (1000 kcal)/24 h. Over a sixty-day period a mean weight loss of 4.6% was achieved. Finger blood-flow (ml/100 ml/min) measured by occlusion plethysmography showed a fall from venous 38.8:t0.9 (mean :tS.E.M.) to 18.7 :t4.3.
Changes in peripheral blood-flow represent an important physiological thermoregulatory mechanism. The decreased finger blood-flow, observed in a thermoneutral environment, could represent an attempt by the body to conserve heat, and therefore energy, in response to energy deprivation. This increased energy conservation would therefore be a contributory factor to the greater than predicted decrease in R.M.R. upon slimming, and would suggest that changes in energy-dissipating mechanisms do indeed occur. Department of Physiology Trinity College, Dublin 2
J. F. JACKSON
ROUTINE MEASUREMENT OF GLYCOSYLATED HÆMOGLOBIN
SIR,-Our experience of chromatographic separation of gly-
cosylated haemoglobins may help others. The difference between glycosylated and non-glycosylated haemoglobins is very small. The attachment of two glucose molecules to the beta-chains does not significantly alter the structure of hoemoglobin but merely neutralises two out of some two hundred titratable groups. The isoelectric point changes by 0.01 pH units. This is the extent of the difference on which the separation of these hemoglobins must be based. It is not surprising, therefore, that a clean separation on minicolumns is difficult. The method is very sensitive to minor variations in technique. We have found that:
(1) Separation on the cation-exchange resins ’Amberlite-IRC 50’ (B.D.H), ’Bio-Rex-70’ (BioRad), and CM-52 cellulose (Whatman) was grossly affected by minor changes in the ionic strength of the eluting buffer, more so than by changes in pH. Most sensitive was CM-52 cellulose, where increasing the ionic strength from 20 mmol/1 phosphate buffer pH 6.70 to 25 mmol/I was the difference between elution of no hoemoglobin and the elution of all hemoglobins. Bio-rex-70 columns behaved similarly, and we found that the "percentage glycosylated ha:moglobin" increased with increasing ionic strength of the eluting buffer. (2) Because proteins can contribute significantly to the ionic 1. James, W. P. T., Davies, H. L., Bailes,
J., Dauncey, P. L. D. Lancet, 1978, i, 1122. 2. Jackson, J. F., Moore, R. E., Tomkin, G. H. IrishJ. med. Sci. 1978, 147, 217.
plastic cannula of a 20-gauge ’Abbocath-T’ intravenous needle to connect the giving set to the fine-bore tubing. This cannula is less likely to perforate the tubing wall at the point of contact if flexion occurs there. As Mr Crow points out (Sept. 23, p. 690) a set comprising guide-wire and fine bore tubing with an attached Luer connection is now commercially available. Patient acceptability has been good, and one man has been inserting his own tube when necessary. An important point in the acceptability of these fine tubes seems to be their ability to allow normal deglutition of ordinary food. We have not found a.constant-rate infusion pump necessary; the limitation of flow-rate provided by the fine diameter of the tubing, as pointed out by Metz et al., is an important factor in the prevention of complications. Severe diarrhoea or gastric stasis can often be overcome by decreasing the dilution of the feeding solutions over a period of 8-10 days. During this time supplementation may be necessary. parenteral This method of feeding is cheaper and safer than parenteral nutrition. Our experience and that of Metz et al. suggests that it should be considered in all patients with an intact gastrointestinal tract who require nutritional supplementation. Department of Surgery, Royal Victoria Infirmary, Newcastle upon Tyne NE 1
A. J. RICH M. E. WHITEHOUSE P. D. WRIGHT
4LI
CONGENITAL INSENSITIVITY TO PAIN AND NALOXONE
Yanagida (Sept. 2, p. 520) is conattempt explain the syndrome of congenital insensitivity to pain by invoking a permanent hyperactivity of an endogenous morphine-like system. However, the naloxone injections should have been done double-blind with placebo control. Moreover, the doses of naloxone (2 and 10 mg) were SIR,-The report from
sistent with
our
Dr
to
large, and we need to know if such doses affect tooth pulp evoked potentials of normal subjects. We used 0.8 mg and sometimes 1.2mg naloxone2after checking that there was no significant effect (on the threshold of the nociceptive flexion reflex of a flexor muscle of the lower limb3) in normal subjects. Our two patients had a classical congenital insensitivity to pain:4 they had lacked pain sensation from birth, the entire body was affected, and all other sensations, particularly thermal sensations, were perceived normally. They could discriminate accurately between hot and cold. Neuropathological examinations failed to reveal any abnormality in the peripheral and central nervous systems.4 In contrast Yanagida’s patient failed to perceive thermal sensations (hot and cold) and had had numerous skeletal fractures resulting in "multiple joint deformities of the Charcot type", as in the cases described by Swansons and by Chatrian et al. This syndrome is called "congenital insensitivity to pain with anhydrosis". In these cases the neuropathologist finds absence of small neurons in the dorsal-root ganglia, lack of small fibres in the dorsal roots, absence of Lissauer tract at all levels in the spinal cord, and reduction in size of the descending tract of the trigeminal nerve in the medulla and cord, with great decrease of small fibres of this tract. "These histologic findings suggest that these patients’ defects in pain and temperature were related to absence, probably due to defective development of small primary sensory neurons, classically believed to subserve these sensations".6 Histologically, therefore, congenital insensitivity to pain and congenital insensitivity to pain with anhydrosis 1. Dehen, H., Willer, J. C., Boureau, F., Cambier, J. Lancet, 1977, ii, 293. 2. Dehen, H., Willer, J C., Cambier, J. Paper presented at the 2nd World Congress on Pain, held m Montreal, in August, 1978. 3. Boureau, F., Willer,J.C., Dauther, C. J. Neuropharmac. 1978, 17, 565. 4. Thrush, D.C. Brain, 1973, 96, 369. 5. Swanson, A. G. ArchsNeurol. 1963, 8, 299. 6. Chatrian, G. E., Farrell, D. F., Canfield, R. C., Reegt, E. L. ibid. 1975, 32, 141 7. Swanson, A. G., Buchan, G. C., Alvord, E. C. ibid. 1965, 12, 12.
Nevertheless, if naloxone does enhance nocievoked potentials in cases such as Yanagida’s this would prompt questions about the relations between the endogenous opiates and the small afferent fibres and the small priare
very different.
ceptive
mary sensory
neurons.
Laboratory of Clinical Neurophysiology, Hôpital Saint-Antoine, 75012 Paris, France; and Department of Clinical Neurology,
Hôpital Beaujon, Clichy
J. C. WILLER H. DEHEN F. BOUREAU J. CAMBIER
ELEVATED METABOLIC RATES IN OBESITY
SIR,-Dr James and his colleagues (Aug. 26, p. 472) confirm the decrease in resting metabolic rate (R.M.R.) upon slimming and comment on the discrepancy between the observed decrease in R.M.R. and that expected from changes in metabolic size. In their original article! they suggest that "energy-dissipating mechanisms appear to be involved". I and my colleagues have studied the thermal responses of five obese females undergoing weight reduction.2 The women were studied in a thermoneutral environment before and during a dietary intake of approximately 4-2 MJ (1000 kcal)/24 h. Over a sixty-day period a mean weight loss of 4.6% was achieved. Finger blood-flow (ml/100 ml/min) measured by occlusion plethysmography showed a fall from venous 38.8:t0.9 (mean :tS.E.M.) to 18.7 :t4.3.
Changes in peripheral blood-flow represent an important physiological thermoregulatory mechanism. The decreased finger blood-flow, observed in a thermoneutral environment, could represent an attempt by the body to conserve heat, and therefore energy, in response to energy deprivation. This increased energy conservation would therefore be a contributory factor to the greater than predicted decrease in R.M.R. upon slimming, and would suggest that changes in energy-dissipating mechanisms do indeed occur. Department of Physiology Trinity College, Dublin 2
J. F. JACKSON
ROUTINE MEASUREMENT OF GLYCOSYLATED HÆMOGLOBIN
SIR,-Our experience of chromatographic separation of gly-
cosylated haemoglobins may help others. The difference between glycosylated and non-glycosylated haemoglobins is very small. The attachment of two glucose molecules to the beta-chains does not significantly alter the structure of hoemoglobin but merely neutralises two out of some two hundred titratable groups. The isoelectric point changes by 0.01 pH units. This is the extent of the difference on which the separation of these hemoglobins must be based. It is not surprising, therefore, that a clean separation on minicolumns is difficult. The method is very sensitive to minor variations in technique. We have found that:
(1) Separation on the cation-exchange resins ’Amberlite-IRC 50’ (B.D.H), ’Bio-Rex-70’ (BioRad), and CM-52 cellulose (Whatman) was grossly affected by minor changes in the ionic strength of the eluting buffer, more so than by changes in pH. Most sensitive was CM-52 cellulose, where increasing the ionic strength from 20 mmol/1 phosphate buffer pH 6.70 to 25 mmol/I was the difference between elution of no hoemoglobin and the elution of all hemoglobins. Bio-rex-70 columns behaved similarly, and we found that the "percentage glycosylated ha:moglobin" increased with increasing ionic strength of the eluting buffer. (2) Because proteins can contribute significantly to the ionic 1. James, W. P. T., Davies, H. L., Bailes,
J., Dauncey, P. L. D. Lancet, 1978, i, 1122. 2. Jackson, J. F., Moore, R. E., Tomkin, G. H. IrishJ. med. Sci. 1978, 147, 217.
