SERUM ALPHA1-ANTITRYPSIN IN CHILDREN WITH BRONCHIOLITIS

1216

veloped. A perforated Meckel’s diverticulum was found at laparotomy and this was removed. She continued to be seriously ill, and on Jan. 17 she was seen by one of us (G.D.O.) Treatment with plasma and blood transfusion improved her general condition, but on Jan. 22 a faecal fistula developed and she was transferred to the General Hospital, Birmingham. On Jan. 25, Clostridium spp and Bacteroides spp were isolated fluid from an abdominal drain, and Escherichia coli and

from

Proteus spp. from her wound. She had required transfusion at the Women’s Hospital, and grouping and cross-matching for this were evidently uneventful. By Jan. 26th she had again become anaemic and blood was needed. At this time mixed-field

agglutination in blood-grouping tests was noticed. The second example was detected in a Kansas City patient who had septic complications of a caesarean section. B. melaninogenicus was grown in blood culture. Although the red cells of both patients were agglutinated by the peanut lectin, they were not agglutinated either by the soya-bean lectin, which reacts powerfully with T-transformed red cells, or by the BS II lectin which reacts powerfully with Tk erythrocytes (table). Agglutination of the red cells of both patients by the peanut lectin was greatly depressed after the cells were treated with papain. Papain has little or no effect on T erythocytes and enhances activity against Tk erythrocytes. Furthermore, the sera of both patients contained anti-T and anti-Tk, and the serum of each patient did not agglutinate the

Beta-adrenergic blocking drugs may induce cold hands and feet and the Raynaud’s phenomenon.23 Our two cases indicate that peripheral gangrene may also develop. White and Udwadia,4 have suggested that alpha-adrenoceptor agonist potentiation by beta-adrenoceptor blockade is the mechanism by which these effects are produced. Beta-adrenegic blocking drugs should be used with caution in patients with peripheral vascular disease.I We thank Dr C. L. Joiner for tient under his care.

allowing us

to

report details of a pa-

J. A. VALE D. B. JEFFERYS

Guy’s Hospital, London SE1 9RT

SERUM ALPHA1-ANTITRYPSIN IN CHILDREN WITH BRONCHIOLITIS

SIR,-A deficiency of alphaantitrypsin (o-A.T.), a major alpha-globulin which in vitro inhibits chymotrypsin, elastase, and neutral protease,5 is a congenital error of metabolism associated with chronic diseases of the respiratory tract and liver.6 Transitory low levels of o-A.T. have been found in newborns with idiopathic respiratory diseases.’ We have stuserum

died o-A.T. in The newborns

from 68 newborn and 29 older children. 15 full-term, 22 premature, and 14 small-

serum were

red cells of the other. The red cells had normal sialic-acid levels and were therefore strongly aggregated by ’polybrene’ (hexadimethrine bromide). We propose the notation Th for this new form of red cell polyagglutination. The microbial basis of exposure of the Th receptor will be the subject of further studies. G. W. G. BIRD Regional Blood Transfusion Service, Birmingham B15 2SG JUNE WINGHAM Community Blood Center of Greater Kansas City, Kansas City, Missouri, U.S.A.

M. L. BECK S. R. PIERCE

General Hospital,

G. D. OATES A. POLLOCK

Birmingham

PERIPHERAL GANGRENE COMPLICATING BETA-BLOCKADE

SIR,-In 1977

we reported a patient with peripheral ganafter she had been prescribed beta-adrenergic blocking grene drugs (propranolol and metoprolol). We have now seen a further patient with this complication. The patient was a 58-year-old woman with a history of moderately severe hypertension. Between 1963 and 1977 she had received a variety of antihypertensive agents including diuretics, methyldopa, bethanidine, and guanoxan..In April, 1977, metoprolol 100 mg twice a day was substituted for guanoxan and she continued to take methyldopa. Within 3 days the patient had intermittent claudication and cold hands and feet for the first time. She accepted these symptoms as part of her disease until October, 1977, when she noticed a purpleblack discoloration of the right 2nd-5th toes. She was seen in outpatients two days later and admitted forthwith. Early gangrene and absent peripheral pulses were confirmed. The patient was advised to stop smoking. Metoprolol was discontinued and dextran, ethanol and phenoxybenzamine were infused. On this regimen the circulation improved, and when she was discharged 2 weeks later all the gangrenous changes had resolved. Since metoprolol was discontinued the patient had not had cold hands and feet, nor has she had intermittent claudication.

1. Vale, J. A., and others Lancet, 1977, ii, 412. 2. Zacharias, F. J., and others Am. Heart J. 1972, 83, 755. 3. Marshall, A. J., Roberts, C. J. C., Barritt, D. W. Br. med.

Serum-«,-A.T. concentrations. A-E newborns: A, full term; B, premature; C, small-for-date; D, with hyaline membrane disease; E, with respiratory aspiration syndrome with or without bronchopneumonia. From F to I older children with: F, upper respiratory infection; G, bronchopneumonia; H, bronchial asthma; I, bronchiolitis. Individual values and mean ± s.D. are shown.

for-date children without acute respiratory disease, 11 with hyaline membrane disease (H.M.D.), and 6 with aspiration syndrome with or without bronchopneumonia. Of the 29 older children, 4 had upper respiratory infection, 7 had bronchopneumonia, 3 had bronchial asthma, and 15 had bronchiolitis. Serum o-A.T. was measured by radial immunodiffusion,-8 In newborn without acute respiratory disease, regardless of gestational age, birth-weight and intrauterine growth rate, the serum o-A.T. concentration was approximately 400 mg/3! (see figure). As reported by others9.10 the mean value in infants White, C. de B., Udwadia, B. P. Br. J. clin. Pharmac. 1975, 2, 99. Ohlsson, K. Scand. J. clin. lab. Invest. 1971, 28, 251. Glasgow, J. F. T., Matthew, F. L., Hercz, A., Levison, H., Sass-Kortsak, A. Am. J. Med. 1973, 54, 181. 7. Evans, H. E., Levi, M., Mandl, I. Am. Rev. resp. Dis. 1970, 101, 359. 8. Mancini, G., Carbonara, A. D., Heremans, J. F. Immunochemistry, 1965, 4. 5. 6.

2, 235. J. 1976, i, 1498.

9. Kotas, R. V., Fazen, L. E., Moore, T. E. J. Pediat. 1972, 10. El Bareesy, M. W., Johnson, A. M. ibid. 579.

81, 593.

1217

(304±75 mg/dl). In infants with aspirasyndrome,
with tion

H.M.D. was

lower

was 348±43 mg/dl which was significantly lower than that in children between 1 month and 9 years of age with upper-respiratory-tract infections (511±90 mg/dl) or bronchopneumonia (512±54 mg/dl) or bronchial asthma (538±114 mg/dl). Kj-A.T. values in bronchiolitis have not been previously

chiolitis, however, a,-A.T. concentration

It is interesting that H.M.D. and bronchiolitis, two infantile conditions which differ in age of onset, aetiology, and pathogenesis, have in common respiratory distress and a low concentration of o-A.T. This globulin appears to rise in respiratory inflammations such as upper airway infections, bronchopneumonia and bronchial asthma, but falls in diseases presenting as bronchiolitis. Bronchiolitis may be a consequenceof the patients’ transitory or congenitally low serum o-A.T. Alternatively, the globulin may be low in the serum because, as in H.M.D.;1it is lost to the bronchial secretions. It would be interesting to know the concentration of OtcA.T. in the bronchial secretions of these patients and what happens to their serum o-A.T. after the acute phase of bronchiolitis.

reported.

Tumour cell from ascitic fluid surrounded

Department of Paediatrics, G. D’Annunzio University,

Chieti, Italy, and C.N.R. Respiratory Virus Centre, Rome

C. DI NARDO G. SABATINO E. BUCCI C. MIDULLA R. MANCINELLI M. MIDULLA

NEUTROPHIL/TUMOUR-CELL ROSETTES IN ASCITIC FLUID OF PATIENT WITH LYMPHOMA

SIR,-Polymorphonuclear leucocytes (P.M.N.) are sometimes in specimens from experimental and human tumours. Their presence could represent non-specific response to tumour-cell necrosis or specific attraction to factors directly or indirectly elaborated by viable tumour cells. A possible mechanism for the participation of P.M.N. in antitumour immunity was suggested by the demonstration of lysis of experimental tumour cells by human P.M.N.1-3 Rosettes, comprised of antibody-coated target cells surrounded by three to eight P.M.N., were observed. 1,2 We report here the observation of tumour-cell/p.M.N. rosettes in vivo, although the role of the rosetting P.M.N. was not defined. Ascitic fluid was obtained from a patient with widespread lymphoma shortly before his death. The patient’s course was protracted over 32years and his tumour was characterised as undifferentiated lymphoid on histology with marked infiltration of P.M.N. both initially seen

and at relapse 2 years later. The figure is a photomicrograph of ascitic fluid removed at the time of recrudescence of abdominal tumour. No organisms were present. The rosette illustrated, a large central mononuclear cell with several nucleoli surrounded by P.M.N., is representative of the large number of these complexes found in the ascitic fluid. Free macrophages were also seen in the ascitic fluid and were distinct from the much larger multinucleolated central cell in the rosettes. These rosettes are very similar to those produced experimentally (see fig. 4, ref. 2). P.M.N. can participate in the immunologically specific or non-specific lysis of tumour cells in vitro.1-3 Most evidence indicates that the effector cell in antibody-dependent cellmediated cytolysis is a monocyte of K lymphocyte.4.5 The observation in this patient and the experiments of Gale and Zighelboim2 suggest that the P.M.N. may be another effector 11. Mathis, R. K., Freier, E. F., Hunt, C. E. New Engl. J. Med. 1973, 288, 59. 1. Gale, R. P., Zighelboim, J. J. Immun. 1974, 113, 1793. 2. Gale, R. P., Zighelboim, J. ibid. 1975, 114, 1047. 3. Clark, R. A., Klebanoff, S. J. J. exp. Med. 1975, 141, 1442. 4. Perlmann, P., Holm, G. Adv. Immun. 1969, 11, 117. 5. Cordier, G., Samarut, C., Brochier, J., Revillard, J. P. Scand. J. Immun. 1976, 5, 233.

by

P.M.N.

cell in antibody-dependent cellular toxicity. Our patient may have mounted a P.M.N.-mediated host response against his tumour, resulting in a prolonged and unusual clinical course. H.T.A. is the recipient of research career development award CA-00075. T.P.S. is an established investigator of the American Heart Association. Supported in part by Public Health Service grant CA18662.

Department of Pediatrics, Harvard Medical School; Division of Hematology-Oncology, Childrens Hospital Medical Center, and Sidney Farber Cancer Institute, Boston, Massachusetts 02115, U.S.A.

HERBERT T. ABELSON THOMAS P. STOSSEL

PLASMA-FLUPHENAZINE CONCENTRATIONS AFTER INJECTION OF LONG-ACTING ESTERS

SIR,-Long-acting esters of fluphenazine (enanthate and decanoate) have been in use for about ten years but their timecourse in plasma has remained undefined, largely because of difficulty with chemical analysis. Since the basis for recommending one ester rather than another is a possible difference in pharmacokinetics we have attempted to clarify this problem by a study with radioactive fluphenazine. Two patients were given fluphenazine enanthate and two received the decanoate. They were informed volunteers. They were given 25 mg (100 fLCi14C) in place of routine non-radioactive doses, and fluphenazine was separated free of its metabolites by selective solvent extraction. 1,2 The figure shows plasma concentrations of fluphenazine. Esters were not detected. The enanthate data are characterised by a smooth rise and fall, with a peak approximately 48 h after the dose, the half-time being 3.6days in one patient and 3.77 days in the other. The decanoate preparation gave more complex data. There was an early high concentration, exceeding anything seen after the enanthate, followed by a rapid fall to a concentration which remained fairly steady at around 0-4 ng/ml until day 6. This plateau was below concentrations obtained with the enanthate at this time. Longer term the decanoate gave the higher concentrations. The half-times of 1. 2.

Whelpton, R., Curry, S. H. J. Pharm. Pharmac. 1976, 28, 869. Whelpton, R., Curry, S. H. Method, Devel. Biochem. 1976, 5, 115.