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METHYLDOPA AND HÆMOLYTIC ANÆMIA
262 revealed a visual acuity of approximately 20/200 bilaterally. The discs were pale and the maculse oedematous, with some pigmentary degeneration. A most interesting and unusual nystagmus of the pendula and roving type was noted; this " " " was followed by a jiggle nystagmus or seesaw nystagmus which was intermittent and appeared when the patient fixed on objects. We are unable to decrease the dose of diodoquin, because the perioral skin lesions become so severe that the patient is unable to maintain nutrition.
manometer, to the method of suspending the manometer in the water container, and to avoiding the possibility of siphoning water into the airway. Department of Anæsthetics, St. Thomas’s Hospital, J. MATHIAS. London, S.E.1.
"
commonly believed that the various substituted oxyquinolines are poorly absorbed and of low toxicity. These experiences suggest that high or protracted dosage can cause optic atrophy. It is
Departments of Pediatrics and Pathology, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
JAMES E. ETHERIDGE, Jr. G. T. STEWART
RESUSCITATION OF THE NEWBORN
SIR,-It is standard practice to treat asphyxia neonatorum with intermittent positive-pressure respiration. The apparatus commonly employed is that described by Barriewhich is effective, inexpensive, and durable. It consists of a source of oxygen, aT-tube water-manometer, and an endotracheal tube. The vertical limb of the manometer is suspended in the water to a desired depth-e.g., 40 cm.-so that the gas pressure in the circuit cannot exceed this figure. The lungs are inflated by intermittent occlusion of a hole near the endotracheal tube. In theory this apparatus cannot deliver a gas pressure greater than 40 cm. of water (or any other pre-determined level). However, it has come to our notice that this supposition is not entirely correct and that, under certain circumstances, excessively high and therefore potentially dangerous pressures can develop within the airway. Firstly, high pressures could be produced by a high flow of oxygen in conjunction with a narrow-bore tube forming the vertical limb of the water-manometer. We have found that a tube with an internal diameter of 3 mm. in a 40 cm. column of water produced a pressure of 92-5 cm. of water when the applied oxygen flow was 25 litres per minute (see accompanying table). This flow-rate is greatly in excess of the recommended flow of 2-3 litres per minute, but it is of the order that could be produced by a faulty pressure-reducing valve. High pressures, per se,
are not
necessarily dangerous, provided they
are not
for longer than half a second, intermittently; but the apparatus should provide adequate safety in all unforeseen circumstances. A tube of 8 mm. diameter, used as the vertical limb of the water-manometer, was proved quite satisfactory.
applied
COMPARISON
OF
OXYGEN-FLOW
RATE
AND
CIRCUIT
PRESSURE
IN
A
NEONATAL RESUSCITATION APPARATUS
METHYLDOPA AND HÆMOLYTIC ANÆMIA Sirwas extremely interested to see the letters from the Committee on Safety of Drugs and from Dr. K. Carstairs and co-workers (Jan. 22) on the possibility that methyldopa (’Aldomet’) causes an autoimmune hxmolytic ansmia. All suspected cases of autoimmune haemolytic ana:mia in the Sheffield region are referred to the Regional Transfusion Centre for serological investigation; over the past three years I have come across 2 cases in hypertensive patients who have been under treatment with aldomet. I am particularly interested in drug-induced haemolytic anaemias, and my suspicions about aldomet were aroused by these 2 cases. The serological findings were very similar to those reported by Dr. Carstairs and co-workers. Both patients gave strong positive direct results in antiglobulin tests, both being of the y-globulin type. So far as I know, both patients recovered after suitable treatment, the 2nd one being taken off aldomet. Regional Blood Transfusion Service, Northfield Road, J. DARNBOROUGH. Sheffield, 10.
ADRENOGENITAL SYNDROME BEFORE BIRTH Sirhave noted with interest the comments made by Mr. Klopper.1 These comments seem to indicate that the methods which have been used in this centre to estimate 17-ketosteroids, 17-hydroxycorticosteroids, and pregnanediol cannot be applied to a different fluid like liquor amnii". In this laboratory the acetylated chromogenic material derived from liquor amnii, in the estimation of pregnanediol, has been shown to have exactly the same chromatographic properties as pregnanediol diacetate. The absorption spectra of the colour produced by liquor fractions taken up in sulphuric acid is also essentially similar to that produced by pure pregnanediol diacetate treated in a similar way. Using the method of Klopper et al. recovery experiments, after the addition of 0.1 mg. and 0.2 mg. amounts of pregnanediol to 60 ml. aliquots of liquor amnii, have indicated that 85-105% of the added material can be recovered. This degree of recovery is similar to that originally described by Klopper2 in his recovery experiments from urine. There is thus presumptive evidence that his method may equally well be applied to liquor amnii without the addition of " many sophisticated improvements ". In an earlier letter3reported on only a small number of estimations of pregnanediol, all completed some time ago. Recent evidence from gas-chromatographic studies, both from the United Sheffield Hospital laboratories4 and elsewhere5 have indicated that the method of Klopper et a1.2 produces a result which is higher than that produced by gas "
chromatography. *
Static conditions.
Secondly, the container for the water should not be closed atmosphere, and a vented stopper is inadequate. Oxygen bubbling vigorously within the container causes the water to rise and occlude a small air-vent, thus causing the airway pressure to rise momentarily. Thirdly, if the water-manometer is positioned so that the water level is higher than the neonate being resuscitated, the water may be siphoned into the airway. To summarise, in using a simple water-manometer device for neonatal resuscitation, particular attention should be paid
from the
to
the diameter of the tubing forming the vertical limb of the 1. Barrie, H. Lancet, 1963, i, 650.
It has been demonstrated that the calculation of values from the peak absorption only-as by Klopper in his original method 2-may result in erroneously high values.4-’ In other methodswhich are used for the estimation of pregnanediol, and which employ the same final colour reaction, a corrective procedure has been introduced for the quantitative evaluation of the sulphuric-acid coloration. One such method used to 1. Klopper, A. Lancet, 1965, ii, 1190. 2. Klopper, A., Michie, A. E., Brown, J. B. J. Endocr. 1955, 12, 209. 3. 4. 5. 6.
Lancet, 1965, ii, 848. Podmore, A. Unpublished. Kirschner, M. A., Lipsett, M. B. Steroids, 1964, 3, 277. Kirschner, M. A., Lipsett, M. B. Gas Chromatography of Steroids in Biological Fluids (edited by M. B. Lipsett); p. 135. New York,
1965. 7. Van der Molen, H. J. ibid. p. 185. 8. Eberlein, W. R., Bongiovanni, A. M. 300.
J. clin. Endocr. Metab. 1958, 18,
manometer, to the method of suspending the manometer in the water container, and to avoiding the possibility of siphoning water into the airway. Department of Anæsthetics, St. Thomas’s Hospital, J. MATHIAS. London, S.E.1.
"
commonly believed that the various substituted oxyquinolines are poorly absorbed and of low toxicity. These experiences suggest that high or protracted dosage can cause optic atrophy. It is
Departments of Pediatrics and Pathology, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
JAMES E. ETHERIDGE, Jr. G. T. STEWART
RESUSCITATION OF THE NEWBORN
SIR,-It is standard practice to treat asphyxia neonatorum with intermittent positive-pressure respiration. The apparatus commonly employed is that described by Barriewhich is effective, inexpensive, and durable. It consists of a source of oxygen, aT-tube water-manometer, and an endotracheal tube. The vertical limb of the manometer is suspended in the water to a desired depth-e.g., 40 cm.-so that the gas pressure in the circuit cannot exceed this figure. The lungs are inflated by intermittent occlusion of a hole near the endotracheal tube. In theory this apparatus cannot deliver a gas pressure greater than 40 cm. of water (or any other pre-determined level). However, it has come to our notice that this supposition is not entirely correct and that, under certain circumstances, excessively high and therefore potentially dangerous pressures can develop within the airway. Firstly, high pressures could be produced by a high flow of oxygen in conjunction with a narrow-bore tube forming the vertical limb of the water-manometer. We have found that a tube with an internal diameter of 3 mm. in a 40 cm. column of water produced a pressure of 92-5 cm. of water when the applied oxygen flow was 25 litres per minute (see accompanying table). This flow-rate is greatly in excess of the recommended flow of 2-3 litres per minute, but it is of the order that could be produced by a faulty pressure-reducing valve. High pressures, per se,
are not
necessarily dangerous, provided they
are not
for longer than half a second, intermittently; but the apparatus should provide adequate safety in all unforeseen circumstances. A tube of 8 mm. diameter, used as the vertical limb of the water-manometer, was proved quite satisfactory.
applied
COMPARISON
OF
OXYGEN-FLOW
RATE
AND
CIRCUIT
PRESSURE
IN
A
NEONATAL RESUSCITATION APPARATUS
METHYLDOPA AND HÆMOLYTIC ANÆMIA Sirwas extremely interested to see the letters from the Committee on Safety of Drugs and from Dr. K. Carstairs and co-workers (Jan. 22) on the possibility that methyldopa (’Aldomet’) causes an autoimmune hxmolytic ansmia. All suspected cases of autoimmune haemolytic ana:mia in the Sheffield region are referred to the Regional Transfusion Centre for serological investigation; over the past three years I have come across 2 cases in hypertensive patients who have been under treatment with aldomet. I am particularly interested in drug-induced haemolytic anaemias, and my suspicions about aldomet were aroused by these 2 cases. The serological findings were very similar to those reported by Dr. Carstairs and co-workers. Both patients gave strong positive direct results in antiglobulin tests, both being of the y-globulin type. So far as I know, both patients recovered after suitable treatment, the 2nd one being taken off aldomet. Regional Blood Transfusion Service, Northfield Road, J. DARNBOROUGH. Sheffield, 10.
ADRENOGENITAL SYNDROME BEFORE BIRTH Sirhave noted with interest the comments made by Mr. Klopper.1 These comments seem to indicate that the methods which have been used in this centre to estimate 17-ketosteroids, 17-hydroxycorticosteroids, and pregnanediol cannot be applied to a different fluid like liquor amnii". In this laboratory the acetylated chromogenic material derived from liquor amnii, in the estimation of pregnanediol, has been shown to have exactly the same chromatographic properties as pregnanediol diacetate. The absorption spectra of the colour produced by liquor fractions taken up in sulphuric acid is also essentially similar to that produced by pure pregnanediol diacetate treated in a similar way. Using the method of Klopper et al. recovery experiments, after the addition of 0.1 mg. and 0.2 mg. amounts of pregnanediol to 60 ml. aliquots of liquor amnii, have indicated that 85-105% of the added material can be recovered. This degree of recovery is similar to that originally described by Klopper2 in his recovery experiments from urine. There is thus presumptive evidence that his method may equally well be applied to liquor amnii without the addition of " many sophisticated improvements ". In an earlier letter3reported on only a small number of estimations of pregnanediol, all completed some time ago. Recent evidence from gas-chromatographic studies, both from the United Sheffield Hospital laboratories4 and elsewhere5 have indicated that the method of Klopper et a1.2 produces a result which is higher than that produced by gas "
chromatography. *
Static conditions.
Secondly, the container for the water should not be closed atmosphere, and a vented stopper is inadequate. Oxygen bubbling vigorously within the container causes the water to rise and occlude a small air-vent, thus causing the airway pressure to rise momentarily. Thirdly, if the water-manometer is positioned so that the water level is higher than the neonate being resuscitated, the water may be siphoned into the airway. To summarise, in using a simple water-manometer device for neonatal resuscitation, particular attention should be paid
from the
to
the diameter of the tubing forming the vertical limb of the 1. Barrie, H. Lancet, 1963, i, 650.
It has been demonstrated that the calculation of values from the peak absorption only-as by Klopper in his original method 2-may result in erroneously high values.4-’ In other methodswhich are used for the estimation of pregnanediol, and which employ the same final colour reaction, a corrective procedure has been introduced for the quantitative evaluation of the sulphuric-acid coloration. One such method used to 1. Klopper, A. Lancet, 1965, ii, 1190. 2. Klopper, A., Michie, A. E., Brown, J. B. J. Endocr. 1955, 12, 209. 3. 4. 5. 6.
Lancet, 1965, ii, 848. Podmore, A. Unpublished. Kirschner, M. A., Lipsett, M. B. Steroids, 1964, 3, 277. Kirschner, M. A., Lipsett, M. B. Gas Chromatography of Steroids in Biological Fluids (edited by M. B. Lipsett); p. 135. New York,
1965. 7. Van der Molen, H. J. ibid. p. 185. 8. Eberlein, W. R., Bongiovanni, A. M. 300.
J. clin. Endocr. Metab. 1958, 18,