378

after

transfusion the granulocyte increments in peripheral blood are not as great as those that result from transfusion of cells collected by centrifugation. Though no truly randomised prospective trial has been reported, granulocyte transfusion is now widely accepted as an essential adjunct to the5 support of patients with neutropenia and infection. The paper by Dr Lowenthal and his colleagues in this issue (p. 353) provides further support for this impression and outlines some of the indications and strictures that should apply. For example, it is essential that granulocytes are transfused in adequate numbers, which may mean that C.G.L. donors are generally preferable to normal subjects. The possible minor functional defect in cells collected from c.G.L. donors is more than offset by the vastly greater number that may be collected. Indeed, a single c.G.L. donor may provide cells for the support of two, three, or more recipients. Moreover, it seems that collected granulocytes retain their bactericidal function for at least 24 hours when stored at 4°C, and so a fraction of the collection can be retained and transfused to the recipient 24 or possibly 48 hours later. It can be difficult to establish objective criteria for assessment of clinical response, and Lowenthal has chosen to look at the patient’s temperature response at 24 hours and 7 days after transfusion and his survival at 20 days; these criteria look very straightforward and are likely to be used by others. Granulocytes collected by centrifugation are inevitably contaminated with numbers of red cells, and in order to prevent haemolysis it seems wise to transfuse granulocytes only to ABO-compatible recipients. On occasion the gravity of the patient’s illness may lead the clinician to break this rule. The importance of HL-A matching is less certain. Certainly granulocyte recovery an hour after transfusion improves in direct proportion to the number of HL-A loci matched between donor and recipient, but a relationship between the degree of HL-A match and clinical Moreover, the response has not been established. great excess of granulocytes that may be available for transfusion when cells are collected from a c.G.L. donor, who is unlikely to share any HL-A loci with an unrelated recipient, may overcome any disadvantage of histoincompatibility. A further unresolved question is whether the collected cells should be irradiated before transfusion. The peripheral blood of patients with C.G.L. contains many cells capable of forming colonies of mature granulocytes in culture in soft agar, and many pluripotent stem-cells may also be present in the blood. Transfusion of C.G.L. cells may thus give rise to bone-marrow allografts in recipients, and this has been confirmed by detection of cells with the Ph’ chromosome in the recipients’ bone-marrow on a number of occasions. Such an allograft is usually rapidly rejected and may be of temporary benefit to the patient. Unfortunately it is occasionally followed by graft-versus-host disease which may prove fatal.7 5. Graw, R. G., Jr., Herzig, G., Perry, S., Henderson, E. S. New Engl. J. Med. 1972, 287, 367. 6. Moore, M. A. S., Williams, N., Metcalf, D. J. natn. Cancer Inst. 1973, 50, 603. 7. Graw, R. G., Jr., Buckner, C. D., Whang-Peng, J., Leventhal, B. G., Krüger, G., Berard, C., Henderson, E. S. Lancet, 1970, ii, 338.

Since the proliferation of lymphoid precursors as well as myeloid cells can be blocked by irradiation of the cells in vitro before transfusion, a wise compromise at present seems to be to irradiate all donations intended for immunosuppressed recipients. Patients with leukaemia who have received a small amount of treatment with cytotoxic drugs may safely be transfused with unirradiated cells.

Granulocyte transfusions do not seem to help febrile patients who are not granulocytopenic. In other words, donor granulocytes will not benefit the infected patient who cannot overcome his infection in spite of an adequate or maximal endogenous marrow response. This may be due in some cases to increased virulence of the infecting organism, but in other cases the fever may not be due to infection at all but to the primary disease. Nevertheless, granulocyte transfusions have become a vital part of the supportive care of leucopenic patients with infection. For this small group of patients they should be readily available, and technical improvements and price reductions should, in the future, make this possible. In this sphere the most important advance of all, still awaited, will be a satisfactory method for long-term storage of granulocytes. LIGHT ON PSORIASIS

MODERN therapies for psoriasis are designed to do what older remedies have been found to do-damp down the heightened rate of epidermal-cell production. Ultraviolet light has been used for many years as an adjunct to topical treatments with tar or dithranol; now Parrish et al.,l from Harvard, have described a modified form of ultraviolet-light treatment which they This is based on the term photochemotherapy. " synergistic action of the photoactive " drug 8methoxypsoralen (methoxsalen) given by mouth and long-wave ultraviolet light (" black light ") in causing epidermal damage. The actual wavelengths used were between 320 and 390 nm., but emission was greatest at 365 nm. with the apparatus that they specially constructed. 21 patients with psoriasis covering at least half the body area who had not responded to various outpatient topical treatments were entered into the trial. None had pustular or guttate psoriasis and no member of the group had psoriatic erythroderma. In 16 of the patients the new treatment was compared to treatment with conventional ultraviolet light alone in a rather ingenious way. They were given methoxsalen (20-50 mg. depending on body-weight) two hours before half their body was exposed to the black-light source. The other half (which was chosen at random) was treated with a conventional ultraviolet light immediately before administration of the oral methoxsalen. The relevant halves were shielded from unwanted irradiation by protective sheets and the exposure times were adjusted so as to maintain a moderate degree of erythema. 5 other patients were treated with methoxsalen and black light only. The 1.

patients in the paired-comparison part of the

Parrish, J. A., Fitzpatrick, T. B., Tenenbaum, L., Pathak, M. A. New Engl. J. Med. 1974, 291, 1207.

379

assessed daily until three independent had observers judged that there was a distinct difference in the two sides. It was found that the test side had improved more than the conventionally treated side after seven to ten treatments, or about two weeks, in every patient. When this clear difference was recognised, the trial was abandoned and the whole body was treated by the black light. The group of 5 patients treated with the new technique alone cleared after twelve to eighteen treatments. All patients remained clear after the trial period, and most were maintained on one to three treatments a week in the outpatient One unavoidable side-effect was a department. uniform increase in pigmentation which seemed " cosmetically pleasing ". There were no really serious or unpleasant side-effects. Three other groups have reported the effects of long-wave ultraviolet light and topically applied psoralens in psoriasis. 2,Of course the principle is essentially the same with topical application as with oral administration of psoralens, but from the reports it seems that topical treatment is less controllable, since the dosages of ultraviolet light required to produce a good effect sometimes cause severe burning (with blister formation) and irregular pigmentation. The nub of the difference in the photochemotherapy method of Parrish et al. is the use of a custom-built powerful source of black light. Of course all who decide to use this new therapy for what is a very common disease must keep a weather eye open for the possibility of toxic effects. Some reassurance on this aspect may be obtained from the fact that the drug (or at least preparations containing it or similar compounds) has been used for vitiligo since the days of ancient Egypt.

study

were

HOSPITAL

PLANNING IN LEEDS ONLY two months ago the Government promised two things relating to the hospital programme in these times of financial stringency-that people would come before buildingsand that everything possible would be done to preserve projects needed to back up medical-school expansion. These undertakings were always incompatible, and sooner or later they were bound to conflict. Now-at St Mary’s, at Birmingham, but most shatteringly at Leeds-it has happened. The regional health authority has said that it cannot see how the rebuilding of Leeds General Infirmary is to be paid for; the Department of Health has promised a final decision as a matter of urgency, but a provisional list of new-building starts for 1975-76 has already been drawn up, and the infirmary is not on it. If the decision is not reversed-and no-one really thinks it will be-this will mean that Leeds General Infirmary does not rank in the top thirty " substantial new building schemes of high priority " promised by the Government when outlining its E255 million hospital programme. There may well be projects that deserve to be above Leeds on social or historical grounds, but two factors-the need for coordination with the medical school and the amount of work done and money spent already-make the 2. Walter, J. F., Voorhees, J. J. Acta derm. vener. 1973, 3. Weber, G. Br. J. Derm. 1974, 90, 317.

53, 469.

harsh and raise broader and purpose of hospital questions has been going on for twelve planning. Planning has already been El 6 million years already; some spent (or is committed) on design and site preparation; at the Department of Health’s insistence the Leeds Hospital for Women has been pulled down, and have been moved, at a capital cost of E318,000, patients " to temporary " accommodation on the outskirts of the city. The new medical school is on the site, but it will need more beds for teaching: the infirmary can take no more than 65 new students each year, while the other big Leeds teaching hospital might handle a few more than its present 65 but could not manage the whole projected expansion of 130 to 216. Management was to have improved on N.H.S. reorganisation a year ago: the lonely E5 million generating plant on the empty Leeds site will be a stark and embarrassing reminder of an episode that has all the makings of a decision

seem

especially

about the

nature

planning nonsense. NEUROBLASTOMA THE prognosis for children with neuroblastoma is extremely poor. Whilst in Wilms’ tumour1 and rhabdomyosarcoma2 combined surgery, radiotherapy, and multiple-drug chemotherapy have enormously improved disease-free-survival rate, the outlook for Unchildren with neuroblastoma is unchanged. not until tumour is often the diagnosed fortunately late in the disease when the patient already has widespread metastases.3 This is despite the fact that neuroblastoma is unique amongst the embryonal tumours of childhood in secreting catecholamines, which can rapidly be detected in the urine by the simple colorimetric Labrosse spot-test in any routine laboratory.4 This simple screening test is rarely carried out until the patient has been subjected to a battery of complex and frequently unnecessary diagnostic tests, even when the diagnosis of metastatic malignant disease is suspected.5 The urinary level of vanillylmandelic acid (V.M.A.) is abnormally high in up to 90% of children with ganglioneuroma, ganglioneuroblastoma, and neuroblastoma.6 Quantitative measurement of the 24-hour excretion of V.M.A. is useful not only in making the diagnosis but also in assessing response to treatment. The previously raised V.M.A. level will fall to normal after successful Children with eradication of localised disease.7 neuroblastoma commonly present with widespread bone metastases in the absence of an obvious primary tumour, and the presenting symptoms tend to be mistaken for rheumatic fever, juvenile rheumatoid arthritis, osteomyelitis, myopathy, or even behaviour problems.5 The finding of a raised V.M.A. together with multiple bone lesions on skeletal survey or malignant cells in the bone-marrow confirms the Sutow, W. W. Cancer, 1973, 32, 1150. Holton, C. P., Chapman, K. E., Lackey, R. W., Hatch, E. I., Baum, E. S., Favara, B. E. ibid. p. 1310. 3. Bond, J. V. Br. med. J. 1972, i, 327. 4. Evans, A. E., Blore, B. A., Hadley, R., Tanindi, S. Pediatrics, 1971, 47, 913. 5. Bond, J. V. Br. J. Hosp. Med. (in the press). 6. Gitlow, S. E., Bertani, L. M., Rausen, A., Gribetz, D., Dziedzic, S. W. Cancer, 1970, 25, 1377. 7. Gitlow, S. E., Dziedzic, L. B., Strauss, L., Greenwood, S. M., Dziedzic, S. W. ibid. 1973, 32, 898. 1. 2.

Editorial: Light on psoriasis.

378 after transfusion the granulocyte increments in peripheral blood are not as great as those that result from transfusion of cells collected by ce...
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