465 TABLE
II—PREVIOUS
CASES
OF ADRENAL
CORTICAL
TUMOUR
proportion was 50 % and 63 % 3- &bgr;-hydroxy-17-ketosteroids.
Our case 2 excreted 12 % of 3-&bgr;-hydroxy-17-ketosteroids although the total output of 17-ketosteroids was 79 mg. per day. The preliminary results obtained by the modification of the assay by Talbot et al. (1940b) are therefore promising for clinical use, but further observations are required to ascertain the lower limit of excretion of 3-&bgr;-hydroxy-ketosteroids in patients with adrenal cortical tumours. SUMMARY
all
In but 2 of the 19 patients the daily output of 17-ketosteroids in the urine exceeds four times the average normal for the age. The first of these 2 is our case 1 in which the output was 14-5 mg. and 20 mg. on successive days. The patient’s age and the fact that she was very ill may account for these low figures, since Fraser et al. found a lower level of excretion in old age, malnutrition and diseases of the liver and gastrointestinal tract. The second case is no. 35 of Fraser et al. Here the low figure is probably due to the urine
having been kept at
room temperature for five years. with virilism or basophilism the output of 17-ketosteroids is usually much lower in those without adrenal cortical tumours. Of 26 cases of virilism and one of basophilism with no adrenal tumours Crooke and Callow (1939) found the output was within the normal range in 14. In the other 13 values up to 35 mg. were found, which is up to about five times the average normal. The 17-ketosteroids output of 10 similar patients (cases 6 to 16, table i) reported in the present paper falls within this range. Similar results were recorded by Talbot et al. (1940b) and by Fraser et al. (1941). Patterson et al. (1942) reported a large series of cases which they divided into postpubertal and prepubertal virilism. In 67 cases in which symptoms commenced after puberty the output of 17-ketosteroids ranged from 6-4 to 33-4 mg. daily, confirming our own results. In 7 cases in which the disease began before puberty, however, the output ranged from 34 to 64 mg. Our case 2, a girl aged 14, falls into this category and had an output of 17-ketosteroids ranging from 79 to 100 mg. Fraser et al. (1941) also described a patient aged 23 (case 42) with virilism and no adrenal tumour who had never menstruated. Her output of 17-ketosteroids was 72-4 mg. per day. Patients with prepubertal virilism without adrenal tumours may, therefore, have a daily output of 17-ketosteroids well within the lower range of those with adrenal cortical tumours, and interpretation of the assays becomes extremely difficult. Further chemical fractionation may assist in the diagnosis of obscure cases. Dehydroisoandrosterone was isolated in relatively large amounts from the 17-ketosteroid fractions of urine of 2 patients with adrenal cortical tumours by Crooke and Callow (1939). Wolfe et al. (1941) isolated in pure form six individual 17-ketosteroids from the urine of a girl with a malignant tumour of the adrenal cortex. They found dehydroisoandrosterone and a transformation product of it to be the main constituents of the mixture, although the other compounds were also present in increased amounts. Dehydroisoandrosterone was also identified in the urine in our case 3, but could not be demonstrated in case 2, in which no tumour was found. This supports the suggestion of Crooke and Callow that identification of this compound gives valuable confirmation of the presence of an adrenal cortical tumour. Talbot et al. (1940b) attempted to increase the specificity of 17-ketosteroid estimation for diagnosis of adrenal tumour by determining the proportion of 3-p-hydroxy-17-ketosteroids in the total fraction. Dehydroisoandrosterone is a member of this group. They found that the 3-&bgr;-hydroxy-17-ketosteroids formed about 10 % of the total for normal men, women or children, while in two girls with adrenal tumours the
Of
’
1. The level of excretion of 17-ketosteroids in the urine of sixteen new patients is reported. 2. Four had adrenal cortical tumours. In three of these the level was at the expected height but in one it was deceptively low. 3. In the other twelve cases adrenal cortical tumours had been suspected but were subsequently believed or shown to be absent. The level was at the expected height in eleven but in one it was deceptively high. This patient had prepubertal virilism. 4. It is suggested that the isolation of dehydroi8oandrosterone from urine or the finding of a high ratio of &bgr;. to (x-ketosteroids in urine is of fundamental importance in the diagnosis of adrenal cortical tumours. We are indebted to Dr. Barsby for case 1, Mr. Alan Brews for case 2, Dr. S. L. Simpson for case 3, Dr. Raymond Greene for case 7, Prof. J. R. Marrack for case 9, and Dr. E. F. Scowen for cases 10 to 16.
patients
REFERENCES
Callow, N. H., Callow, R. K., Emmens, C. W. (1938) Biochem. J. 32, 1312. and Stroud, S. W. (1939) J. Endocrinol. 1, 99. Crooke, A. C. and Callow, R. K. (1939) Quart. J. Med. 8, 233. Fraser, R. W., Forbes, A. P., Albright, F., Sulkowitch, H., Reifenstein, E. C. (1941) J. clin. Endocrinol. 1, 234. Friedgood, H. B., Whidden, H. L. (1939) New Engl. J. Med. 220, 736. Patterson, J., McPhee, I. M., Greenwood, A. W. (1942) Brit. med. J. i, 35. Talbot, N. B., Butler, A. M., Berman, R. A. (1942) J. clin. Invest. 21, 559. MacLachlan, E. A. (1940a) J. biol. Chem. 132, 595; (1940b) New Engl. J. Med. 223, 369. Wolfe, J. M., Fraser, L. F., Friedgood, H. B. (1941) J. Amer. chem. Soc. 63, 582. -
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PRESSURE MEASUREMENT IN SMALL ANATOMICAL CAVITIES DAVID
S’. EVANS
PH D CAMB.
Clarendon
K. MENDELSSOHN
*
PH D BERLIN
Laboratory, Oxford
MEASURES of pressure changes in small anatomical cavities, such as the sinuses of the ear, are useful-in many investigations, particularly those of aviation medicine. If the volume of such cavities is of the order of 1-2 c.cm. or less, direct measurement with an ordinary pressure gauge, which has a considerable dead volume, will yield results containing an error which cannot be corrected, for the pressure change occurring in the whole system of cavity plus manometer-due, - say, to a variation in barometric pressure-will be very different from the change which would have taken place in the cavity alone. The adoption of a null method to avoid this error is often not justified by the considerable experimental complications involved. It therefore seems of value to describe a simple device which we have used for such determinations, and which gives a direct reading of the pressure in an- air-filled cavity, while eliminating almost completely the error due to dead volume. It consists of an ordinary Bourdontype manometer which is connected by a flexible metal tube to a hypodermic needle. The whole dead volume of the device is taken up by a liquid of low vapour pressure. The needle can be sealed into the’’cavity, and since the compressibility of the liquid can be neglected, the manometer will give a faithful record of the pressure changes in the cavity. The only error in this method is introduced by the volume change which the spiral of the Bourdon gauge undergoes over the range of pressures under consideration. This change is small, and in the case of the gauge we use-an ordinary industrial manometer of 2 in. scale diameter-amounted to only 0-03 * Working with a personal grant from the Medical Research Council.
466 for the whole range between vacuum and atmospressure. The liquid used for filling was butyl phthalate, which.. has a vapour pressure of less than 10-3 mm. Hg at ordinary temperatures ; but any other liquid with a low vapour pressure would serve. The method of filling the device is shown in fig. 1. A wide T-tube with a ground-glass stopper at the top was c.cm.
pheric
-
connected
to
a
introduced, and
for 2-3 hours to the complete removal of the considerable quantity of occluded gas which is usually present in s u c h
pumped ensure
liquids as supplied commercially. Then the needle was pushed up through the Fig. I-Method of filling manometer. rubber cap until its point protruded above the liquid level, and the air was pumped out of the needle and gauge. The needle point was then withdrawn below the liquid level, and air slowly admitted through the pumping lead, so that the air pressure forced the butyl phthalate through the needle until the device was quite full. Then the needle was pushed up again above the liquid level, and the pressure lowered to the minimum expected in the experiments. This was done in order to remove the surplus
which otherwise would have been forced out into the the slight contraction of the Bourdon spiral as the pressure was lowered. The pressure was then allowed to rise slowly to atmospheric, and the needle was withdrawn readv for use. When using the device on the sinus of the ear we found it convenient to seal the
liquid,
cavity by
needle into the
IN INDIAN PATIENTS
M. V. GOVINDASWAMY M B
MYSORE, SUPERINTENDENT,
D PM
BANGALORE
MENTAL HOSPITAL
B. N. BALAKRISHNA RAO M B
BOMBAY,
F R C S
PROFESSOR OF SURGERY, MYSORE UNIVERSITY
vacuum
pump. Any good rotary pump will serve. The lower end of the T-tube was closed by means of a rubber cap of the type used for sealing ampoules. A ’thin coat of shellac applied to the glass just before the cap was slipped on ensured a joint. A few vacuum-tight E c.cm. of butyl phthalate, sufficient to fill the device, were
BILATERAL PREFRONTAL LEUCOTOMY
THIS paper reports the results of bilateral prefrontal in 25 patients in the Mysore Government Mental Hospital, Bangalore, South India. The climate, diet, social and economic conditions of the people in India differ from those in western countries, and the differences are reflected in bodily health and psychological characteristics ; these in turn influence the symptomatology of mental illnesses, and their response to treatment. On the psychological side patients often show elation, restlessness, volubility, hyperactivity, hallucinosis and behaviour disorders ; on the physical side, lack of growth, anaemia, avitaminosis and dehydration. Confused and delirious states are not only common in themselves but also complicate the affective and schizophrenic reaction types. As reported by one of us1 the same disabilities are probably responsible for the variable responses to methods of treatment, especially shock therapy. Unexpected variations in blood-sugar, hepatic deficiencies and poverty of the bone-marrow all seem to contribute towards the greater incidence of " after-shock " during insulin therapy, and to unpredictable fits of unconsciousness both during insulin therapy and induced leptazol convulsions. Hence the treatment found to be of the maximum benefit to patients, and gradually developed at this hospital, has been attention to the physical condition of the patients irrespective of reaction types, especially the treatment of dehydration and chronic starvation. If shock therapy is decided upon subsequently, sub-shock doses of insulin followed by intravenous ammonium chloride, 5-10 c.cm. of a 10 % solution, are administered. Leptazol is substituted if ammonium chloride is ineffective. - This routine treatment has yielded the best results, and there havebeen no untoward
leucotomy
complications.
With these differences between Indian and European our experiences of the results of preon Indian patients may be of interest.
patients in mind, frontal leucotomy
ADAPTER
flange (fig. 2). The adapter was first cemented into a hole drilled in the bony wall of the sinus, the flange being used to make a reliable seal. The needle was then inserted through the hole of the adapter, into which it fitted closely, and sealed to it with a drop ofApiezon (W) ’ wax. To prevent air rising as a bubble into the manometer
TECHNIQUE All patients selected have been physically healthy, between the ages of 22 and 35 ;_; 19 were men and 6 women. The duration of the disorder was from 3 to 7 years. In some shock therapy had been tried without benefit. Most of them were schizophrenics, but in a few it was felt that schizophrenic symptoms had probably been superimposed on a’ primarily affective disorder. Since the patients had been ill for years, symptoms usually associated with chronicity were present in most. Stereotypy, automatisms, childishness, volubility, lack of initiative, offensive habits, were not regarded as contra-indications: on the contrary, they were deliberately sought because it is in cases with such symptoms that the chances of recovery, whether spontaneous or due to treatment, are remote. The patients had different educational, intellectual and social backgrounds, and since they were all chronic
we
no
b
o
n
e
with the aid of a small metal
adapter,
in the form of a narrow
bore tube with a
have found it advisable to bend the needle and flexible tube as shown in fig. 2. It should be noted that since a Bourdon gauge records the difference between the external and internal pressures, the readings must be combined with the barometric pressure to which the gauge is exposed, if absolute values are required. In addition; if the gauge and the needle are at very different levels a correction for the hydrostatic pressure of the liquid column in the connecting tube must be applied. We should like to express our thanks to Mr. Victor L. Bradfield for the loan of dental drilling equipment.
Dr. K. F. KITCHIN will introduce a series of discussions on the elements of Jungian psychology on Wednesdays, at 5.4S PM, from April 19 to June 7, at the University of London Club, 21, Gower Street, W.C.I. Further particulars from the secretary of the Guild of Pastoral Psychology, 1, Rutland Grove, W.6.
SELECTION AND
uniform, planned psychometric investigation was Binet-Simon tests, Porteus mazes,. and the
possible.
memory tests advocated by Cattell, Shakow and Roe were administered where possible, and administered again after operation. A detailed history was not available in many cases. ’Sodium Amytal’is given before operation to patients who are inclined to be agitated and nervous. Chloroform by the open method is used both for induction and maintenance. A point 3 cm. behind the anterior orbital margin and 5 cm. abovee the zygoma is marked, and an oblique incision, 5 cm. long, is made with the marked point at its centre. In the first 6 cases a trephine opening was made in the skull, but later a 1 em. diameter burr-hole was made, lying just in front of the anterior branch of the middle meningeal artery. In most of our cases no pulsation of the dura could be seen ; in 5 there 1.
Govindaswamy, M. V. Lancet, 1939, i,
506 and 1232.
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