MEDICAL EMIGRATION AMONG BIRMINGHAM GRADUATES

1277 cervical arthritis. X-ray examination showed a certain of cervical arthritis, so I sent him to an orthoptdic surgeon, who wrote to say that he could not remember a similar case, but he arranged for him to have treatment by due

to

amount

medically qualified osteopath. This treatment had no effect, and I gave him 6 intramuscular injections of phenylbutazone (he had a history of previous peptic ulcer, and I thought it safer to give him 3 ml. of the solution intramuscularly). After each injection he remained completely free from pain for periods up to 48 hours, but, as the effect was only transient, I persuaded him to see the laryngologist again, who then found a carcinoma in the crico-arytenoid fold. Biopsy showed an invasive and highly malignant squamous-cell carcinoma. He was treated with irradiation from the cobalt bomb, and the last report I had stated that the growth had entirely disappeared, and that there were no nodes in the neck. The patient had none of the usual side-effects of cobalt irradiation, and the question arises whether phenylbutazone has been of any value as an ancillary to recognised treatment. It is a valuable drug in all kinds of inflammation, and I wonder whether it has any part to play in carcinomatosis, if only as an a

Chromosome analysis

on

peripheral blood-culture

gave a

modal number of 48: 45 46 47 48 No. of chromosomes 1 No. of cells1 3 34 Twenty modal metaphase plates were karyotyped, and all showed 17 chromosomes in the group 6-X-12 and 5 chromosomes in the group 17-18 (see accompanying figure). Feulgenstained buccal smears and sections of skin demonstrated ,nuclei with two Barr bodies. The chromosomal and cyto......

logical findings

consistent with

are

a

XXX

trisomy 17/18

constitution. A detailed report will be

published later.

Istituto di Patologia Medica, Università di Ferrara, Italy. Istituto Provinciale per l’Infanzia,

Ferrara, Italy.

QUICKER

N. RICCI. L. BORGATTI

CHROMOSOME ANALYSIS

SIR,-Owing to the time-consuming work involved in karyotyping, chromosome analysis often proceeds at a rate insufficient to meet clinical needs and inadequate for statistically designed population studies. In order to examine more accurately the chromosome samples as well as to decrease significantly the time required for analyses, we are in the process of developing a relatively inexpensive and readily available semi-automatic recognition system. In a pilot study designed to evaluate the basic instrument, a programme was written to count and classify, in a simple way, a small section of a photographed chromosome spread. This procedure correctly counted and listed the seven chromosomes in the area selected and ignored all irrelevant spots. Our method was, therefore, able to interpret the information correctly and to ignore all the noise generated in the process. We expect with further refinement to develop a scanning system which will be directly connected to the microscope. This procedure will permit the direct recording from the slide of chromosome information on to magnetic tape in digital form and analysis of the data by means of a pattern recognition programme on a general-purpose digital computer. Department of Medical Genetics, New York State Psychiatric Institute, ARTHUR FALEK. Columbia University, New York. Medical Science Department, Avco

Corporation,

Research and Advanced

Development Division, Wilmington, Mass.

PETER W. NEURATH.

PHENYLBUTAZONE AND RADIOTHERAPY clinical observations are of no real value unless correlated with the experience of others-which is why I think this case may be worth recording.

SIR,-Casual

A man of 60 complained of intense pain in the ear on yawning opening his mouth widely. I could find nothing wrong and I sent him to a laryngologist, who reported that he also could find nothing amiss, but wondered whether the pain could be or

agent for the relief of

pain. CHRISTOPHER HOWARD.

MEDICAL EMIGRATION AMONG BIRMINGHAM GRADUATES

SIR,-As a result of the study by Dr. Whitfield (Oct. 26) of the present location of doctors who graduated from Birmingham medical school between 1948 and 1958 you .suggested in your annotation that about 140 medical graduates emigrate from Britain annually. The estimate of 140 medical emigrants per year rests on assumptions of doubtful validity and may greatly understate the rate prevailing in recent years. Dr. Whitfield’s study does not provide figures of total medical emigration from Birmingham in recent years-it only provides figures of emigration for a sample of Birmingham medical graduates selected by year of graduation. The number of doctors who graduated from Birmingham medical school between the years 1948 and 1958 and have since emigrated has been accurately ascertained, but emigration since 1948 of all doctors from Birmingham who graduated before 1948 and after 1958 has been excluded. Although 9-5% of the graduates of 1948-58 have already emigrated it is illogical to assume, as you appear to have done, that emigration in recent years has been equivalent to 9-5% of the output of the medical school. An unknown number of graduates who qualified in the 1950s will emigrate in the future and it will be many years before it can be known what proportion of any one year’s graduates have emigrated. But even if, as Dr. Whitfield suggests, a fairly constant proportion of each year’s graduates emigrate, it does not follow that that particular proportion emigrates each year. It is indeed clear from Dr. Whitfield’s paper that the rate of emigration of Birmingham graduates is rising rapidly and now far exceeds 9-5% of the output of the medical school. He pointed out that " there seems little doubt that emigration among Birmingham medical graduates is increasing ", and 50 of the 92 graduates in his study who have. emigrated left in the past three years. Emigration during 1960-62 of only those graduates studied by Dr. Whitfield has thus been at the rate of 20% of the output of the medical school. (In the three years 1960-62 about 250 Birmingham medical students graduated, and 50 of the Birmingham graduates of Dr. Whitfield’s study emigrated.) If all the Birmingham graduates who emigrated in 1960-62 were included the rate could well be within the 25-33 % range which I have suggested has recently applied to British medical graduates as a whole. But this high rate is a new phenomenon and certainly did not prevail in the 1930s and 1940s. The rapidly rising rate of medical emigration from Birming-

1278 of the ratio of 9-5% an arbitrary basis for you have done, that 140 doctors annually estimating, emigrate from Britain. The size of the ratio which you have used varies greatly according to the year in which it is calculated. From fig. 2 in Dr. Whitfield’s paper it can be deduced that by 1960 only 4-3% of those who graduated between 1948 and 1958 had emigrated; by 1961 the proportion rose to 6-1%, by 1962 to 7-9%, and by 1963 to 9-5%. By using the 1963 figure you state that " if the Birmingham figures are repre140 or so (medical graduates from Britain) may sentative be expected to emigrate within five to fifteen years of their graduation ". Equally, if the 1960 figure had been used one could have said that only about 70 might have been expected to emigrate within two to twelve years of graduating. Such calculations give no meaningful information about the rate of

of the wound, and application of tight pressure and ice-bags. On March 8, a device was constructed as shown in the accompanying figure. One ampoule of topical thrombin (Parke-Davis) was dissolved in 500 ml. of physiological saline solution and placed in a blood-transfusion bottle. A thin plastic tube was connected to the bottle and the other end was connected by means of a Y-adaptor to two tubes, each 2 mm. in diameter. The ends of these were heat-sealed, and multiple minute openings made in the narrow tubes over a length equal to the length of the wound. Each of the two perforated tubings was placed under the upper and lower flap of the amputated thigh. This continuous drip of topical thrombin into the redressed wound area soon stopped the bleeding. The tubes were removed after the wound had healed sufficiently. The patient was fitted with an artificial limb and returned home.

medical emisration from Britain.

The time-honoured, generally accepted method of haemostasis in congenital coagulation-factor deficiencies is to supply the missing factor to the general circulation of the patient. The real need for it may at times be circumscribed as in the case described or in haemarthroses. Sawyer et al. 3reported on the successful application of a D.c. electric current to an area of bleeding in haemophilics. Their method and ours could serve as starting-points for further development of local hxmostatic measures in bleeding due to deficiency of plasma coagulation factors.

ham renders the

use

as

...

JOHN SEALE. POSTOPERATIVE HÆMOSTASIS IN CONGENITAL BLEEDING DISORDERS SiR,ŃThis report is based on successful haemostasis after thigh amputation in a patient with congenital factor-ix deficiency. The principle of the method may be equally well applied to patients with single or multiple deficiencies of coagulation factors. It is based on continuous irrigation of the wound with a weak thrombin solution substituting for any factor participating in thrombin formation. In afibrino-

genaemia a fibrinogen solution

equally

would be successful.

The patient, year-old Negro

27-

a

male

with a previously diagnosed familial factor-ix deficiency, was admitted to one of the Medical College of Vir-

ginia hospitals

on

Feb. 19, 1960, from an outlying area. His left shin was injured 57 days before admission. The wound was infected, the leg was gangrenous, and the wound bled uncontrollably. The patient was transferred to us

i

Continuous drip device for with thrombin solution.

irrigation

with a tourniquet applied to the mid-thigh and the leg placed in ice. This made amputation an immediate necessity. His hemoglobin was 69 g. per 100 ml., white-cell count 11,500, Quick’s prothrombin test 100%, individual coagulation factor assays in normal range, including factor vm of 97% (Brinkhous’s method).l The thromboplastin generation test (T.G.T.) (Biggs and Macfarlane 2) gave the following results: control 10 sec., patient’s serum 30 sec., whereas the patient’s

aluminium-hydroxide-adsorbed plasma and platelets were normally active in this test system. After blood-transfusions, the patient’s haemoglobin concentration increased to 11 g. per 100 ml. and T.G.T. shortened to 16 sec. Mid-thigh amputation was performed on Feb. 20 with some excessive bleeding from the muscles during the operation. The early postoperative course was uneventful, but when the drains were removed from the wound on Feb. 25, bright-red blood began to ooze from the incision. Daily blood-transfusions were needed to keep up with his bloodloss, but bleeding continued despite transfusions, redressing R. D.,

R.

K.

M., cited in Methods of

H., Brmkhous, Wagner, 1 Langdell, Study (edited by L. M. Tocantins), p 72. New York, 1955. Biggs, R., Macfarlane, R. G Human Blood-Coagulation and its orders; p 401 Oxford, 1953.

2.

Dis-

Division of Clinical Pathology, Medical College of Virginia, Richmond, Virginia, U.S.A.

HENRY G. KUPFER.

METHYL-HYDRAZINE IN MALIGNANT DISEASE SIR,-We were very interested in the article by Professor Mathe and others (Nov. 23) because we too have begun a trial with this new cytotoxic drug in advanced malignancy. We would have welcomed more details of the dosage, which was stated in the text to be 200-500 mg. orally or intravenously, but in figs. 1 and 3 it was given as 250 mg. intra-arterially. We have employed a different scheme after consultation with Dr. W. Bollag, of Basle, who was the first to use this drug. We start with 250 mg. intravenously. Next day we give 500 mg. and on the third day 1000 mg. We then continue with 1000 mg. on alternate days to a total of 3-75 g. for the reticuloses, or 5-75 g. for solid tumours. We have left an interval of three weeks between the intensive initial therapy and the maintenance doses of 100 mg. orally three times a day. This treatment is governed by the leucopenia induced, which, in those cases where treatment has had to be stopped, lasted no more than a week. To avoid the intense nausea and vomiting that follow the injection, we found that small doses (25 mg.) of promazine (’Sparine’) given 30 minutes previously are all that is necessary. When we tried larger doses of promazine, instead of the pyridoxine advised by the manufacturers, semicoma followed. We can only presume that there was a synergistic response.

Although we can confirm the benefits of methylhydrazine we wish to add a word of caution before this treatment becomes widespread and perhaps falls into disrepute. Although late cases of Hodgkin’s disease have responded, there is no reason to suppose that this is yet the treatment which should replace more firmly established cytotoxic agents. Far more work is required on the best method of administration and dosage and on the long-term comparison with alkylating agents. Further, the possibility of late sequelae is as yet unknown; this is a drug which has been on trial for too short a time for adequate assessment. These considerations led us to use methyl-hydrazine only in advanced cases which had failed, or ceased, to respond other methods of treatment. Our results with various other tumours have so far not been very striking, although

to

3. 4.

Sawyer, P. N., Wesolowski, S. A. Irish J. med. Sci. 1963, 438, 255. Sawyer, P. N., Dennis, C., Wesolowski, S. A. Ann. Surg. 1961, 154, 556.