1340

She had also taken chlordiazepoxide (’ Librium ’) for six

weeks, tetracycline (’ Achromycin ’) for three weeks, and

ampicillin (’Penbritin’) for seven days. The serum-bilirubinrose to 54 mg. per 100 ml., the alkaline phosphatase to

31 King-Armstrong units, and the serum-glutamic-pyruvictransaminase to 730 units. Liver biopsy showed severe cyto-plasmic degeneration of the parenchymal cells, with polymorphand eosinophilic cellular infiltration around the portal tracts.All drugs were withdrawn; the patient slowly recovered andhas remained well. Although this illness was probably due todrug therapy, it is impossible to be sure which of the four drugswas the cause. One other case of jaundice, possibly due tochlordiazepoxide, was described by Cacioppo and Merlis 2;no case of jaundice attributable to guanoxan has so far beenseen during trials in which over 300 patients have been treated.3

Like Peart and MacMahon,l we believe that guanoxanis a valuable drug in hypertension, particularly when thisis severe or resistant to other compounds. The gastro-intestinal side-effects, although troublesome, can in mostcases be tolerated or overcome.

E. MONTUSCHIT. W. I. LOVEL.

Hypertension Clinic,Whittington Hospital,

Highgate Hill,London, N.19.

BETA-RECEPTOR BLOCKADE IN THE DIAGNOSIS

OF PHÆOCHROMOCYTOMA

R. L. HODGE.University College Hospital

Medical School,London, W.C.1.

SIR,—The diagnosis of some cases of phaeochromo-cytoma undoubtedly presents difficulty, despite thebiochemical and pharmacological tests available; hencenew diagnostic aids are always of interest. It is difficultto see, however, what advance on current methods the testsuggested by Dr. Paton (Nov. 21) represents, particularlysince pharmacological tests are declining in importancein relation to modern chemical tests. Furthermore, if thetest is carried out on patients with a blood-pressure of150/100 mm. Hg or less, as recommended, they are oneof the groups least likely to show a rise in pressure withP-blockers.

Since pronethalol can cause extensive carcinoma in

mice, it should never be given to man.

EOSINOPHILIC LEUKÆMIA WITH

Ph1-POSITIVE CELLS

GEORGE L. KAUER, Jr.RALPH L. ENGLE, Jr.

The New York Hospital/CornellUniversity Medical Center,New York, N.Y., U.S.A.

SIR,-A recent report 4 of two cases of eosinophilicleukxmia in which the PhI chromosome was lackingprompts this report of a patient with eosinophilic leukxmia,confirmed at necropsy, whose cells were PhI-positive.A 45-year-old man with anxmia and leucocytosis of 38,000

per c.mm. had an enlarged spleen removed at another hospitalduring an exploratory operation. Because of a diagnosis of" myelogenous leukaemia", he was treated with methyl-prednisolone and 6-mercaptopurine. He was admitted to theNew York Hospital about a year later when his hxmoglobinwas 12.4 g. per 100 ml., haematocrit 33%, and white blood-cells132,000 per c.mm. with 83% eosinophils. The bone-marrowwas distinctly hypercellular with a myeloid/erythroid ratio of20:1. Half the myeloid cells were eosinophilic. The leucocyte-alkaline-phosphatase score was 2 and 3 on two determinations,with a normal range of 40 to 60 units. He received busulphan,which was stopped after 24 days on account of severe thrombo-cytopenia. His white-blood-cell count was then 44,000 perc.mm., but it later rose to 256,000 per c.mm. with 79%eosinophils.The patient’s course was complicated by refractory cardiac

failure, cardiac arrhythmias, and a hxmorrhagic pleural effusion.In addition to the intensive therapy for the cardiac failure and2. Cacioppo, J., Merlis, S. Amer. J. Psychiat. 1961, 117, 1040.3. Clinical Research Department, Pfizer Ltd. Personal communication,

1964.4. Krauss, S., Sokal, J. E., Sandberg, A. A. Ann. intern. Med. 1964, 61, 625.

the busulphan, the patient received numerous blood-trans-fusions, prednisone, and a short course of 6-mercaptopurine.Two chromosome studies by peripheral blood-culture b

performed 6 weeks apart showed only a few readable spreads,but 4 out of 6 cells showed the Ph! chromosome. These studieswere done after the busulphan, methylprednisolone, and initial6-mercaptopurine therapy, but before the prednisone andsecond course of 6-mercaptopurine therapy.

This work was supported by the Health Research Council of theCity of New York under contract no. U-1178.

CYTOTOXIC DRUGS IN BRONCHIAL CARCINOMA

SIR,-The article by Dr. Grenville-Mathers and Dr.Trenchard (Dec. 5) shows how Armitage’s sequentialmethod of analysis permits an assessment of cytotoxicdrugs on a small number of patients. This method can beextended to cover the use of such drugs in lymphoreticulardisease, as shown by a trial at the Christie Hospital,Manchester.The purpose of the trial was to compare vinblastine sulphate

with mustine. To provide a basis for comparison, all patientswith late Hodgkin’s disease who had had mustine as their firstcourse of chemotherapy between the years 1955 and 1960 werestudied. These patients, 67 in all, were divided by age intothree groups-0-30 years, 31-50 years, and over 50 years.Further subdivision by sex produced a total of six groups. Thesubjective duration of remission was recorded for each case.From December, 1962, onwards each patient with late Hodg-kin’s disease coming for chemotherapy for the first time wastreated with vinblastine. The dosage of this drug (0-4 mg. perkg. body-weight)given intravenouslyin two doses on suc-cessive days was

identical with thatof mustine. Eachvinblastine case wasmatched (by draw-ing an envelope)with a case from the

corresponding age-and-sex group inthe mustine series.The results plottedon the accompany-ing figure, in whichthe line moves up-wards for a result

favouring mustineand downwards for

vinblastine, showthat there was no

significant differencebetween the groups-this answer being obtained with 17 pairs.So, if this evidence is accepted, when it comes to a choicebetween mustine and vinblastine in late Hodgkin’s disease,factors other than the potential duration of the remission willdecide the issue.This trial, as well as that of Dr. Grenville-Mathers and Dr.

Trenchard, may be criticised for its use of retrospectivematerial. But with a condition such as Hodgkin’s disease, inwhich response to treatment differs quite widely from one groupto another (in the mustine series the average length of remissionvaried between five months for women under thirty years ofage to six weeks for men in the 31-50 age-group), either a largenumber of cases must be used (so that differences may beexpected to even themselves out) or cases must be matched inpairs before they are included in a trial. The first alternative is5. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M.,

Hungerford, D. A. Exp. Cell Res. 1960, 20, 613.