504 provement, which remained and was increased after each dose. His cumulative improvement has been sustained and dramatic: he now easily turns over, gets out of bed, walks 6 miles daily, does a push-up and deep-knee bend, climbs 120 steps, and holds a heavy chair over his head. Distal muscles of finger function have improved, but not strikingly so far. Interferon levels increased from zero to 100-500 units with each polyI.C.L.c. dose. C.S.F. protein is now 36 mg/dl and motor-nerve conduction velocity is 40 m/s in the median nerve and 27 in the ulnar. In the three polY-I.c.L.c.-treated patients, leucocytes were studied with each dose (39 total doses), usually thrice daily for 2 days and then daily until the next dose (more than 250 studies altogether). All three responded similarly. Lymphocytes fell to 17% of baseline, having a nadir in 1-2 days, and returned to baseline by the 4th or 5th day; the granulocyte response was biphasic, with a 3-fold rise at 6-24 h, a 30% fall from baseline at 2-3 days, and return to baseline by 3-5 days. We propose that POlY-I.C.L.C. has been responsible for the striking clinical improvement of this patient and that this benefit may have been the result of an "anti-dysimmune" action of poly-l.c.L.c. acting by lymphocyte suppression rather than increasing interferon or stress-induced corticoids. POlY-I.C.L.C. would then be a new type of immunosuppressant drug potentially beneficial in other kinds of dysimmune diseases (and perhaps in lymphocytoproliferative disorders). If it acts through interferon, POlY-I.C.L.C. would provide new insight into the pathogenesis of relapsing neuropathy and a new treatment. Medical Neurology Branch, National Institute of Neurological and Communicative Disorders, National Institutes of Health, Bethesda, Maryland 20014, U.S.A.
W. KING ENGEL RICHARD A. CUNEO HILTON B. LEVY
A.L.G. IN APLASTIC ANÆMIA
S!R,—The preliminary report by Speck et al. on the use of antilymphocyte globulin (A.L.G.) with or without partially compatible bone-marrow for treating severe aplastic anaemia is intriguing. However, as Speck et al. say, aplastic anaemia, even when severe, has a variable course. Thus, to assess the contribution of A.L.G. to survival, a control group treated identically except for A.L.G. is required. The controls and A.L.G. treated patients should be comparable in disease severity, interval from diagnosis to entry into study, and other factors, such as age, sex, and infection, that may affect survival. In the absence of concurrent controls, results of relatively small series may be misleading. For example, the trials of A.L.G. + incompatible marrow by Mathe et awl. were uncontrolled. Survival of 5/24 patients treated in this manner is no different than the survival of patients with severe aplastic anaemia receiving supportive care alone.3 Similarly, early uncontrolled reports of improved survival with androgen therapy for severe aplastic anaemia were not confirmed when these agents were evaluated in a controlled trial.4.5 Speck et al. recognise the limitations of their work. I hope that they will design follow-up trials to define the role of A.L.G. in treating severe aplastic anaemia. Department of Pediatrics, Midwest Children’s Cancer Center, Milwaukee Children’s Hospital, Milwaukee, Wisconsin 3233, U.S.A.
1.
Speck, B., Gluckman, E., Haak, H. L.,
BRUCE M. CAMITTA
van
ANTI-HBs IMMUNE GLOBULIN TO PREVENT HEPATITIS B
SiR,—Frosner et al.’ described three cases of hepatitis, after sexual contact or accidental needlestick exposure, despite administration of anti-HBs immune globulin (H.B.I.G.). They concluded that H.B.I.G. had not prevented hepatitis B but had merely extended the incubation period. We disagree with this conclusion, especially for the third case. If H.B.I.G. failed in the first two cases, it was probably because prophylaxis was attempted too late after exposure (12 days or more in the first case of sexual contact and 15 days in the second case). Such cases are not really failures of im-
munotherapy. In the third case, hepatitis B in a nurse 205 days after needlestick exposure, a second, undetected exposure 2-4 months after the detected incident is the more likely explanation. We have seen a similar case (hepatitis B 6 months after exposure and H.B.I.G.).3,4 This case was interpreted as a later, undetected contamination. The permanent exposure risk in haunodialysis units was the incentive for us to try repeated H.B.I.G. injections to achieve permanent protection.3,4 We have found that 5 ml H.B.LG., with the same activity as the international reference, protects for only 2 months5 despite weak levels of passive anti-HBs beyond this period. This residual anti-HBs is too weak to guarantee effective protection. In our experience H.B.I.G. prevents hepatitis B if the H.B.I.G. titre is at least as potent as the international reference, the dose is 0-08 ml/kg, the injection is given no more than 8 days after exposure, and the H.B.I.G. injections are repeated every 2 months if the risk of exposure is great and permanent. ’
Etablissement Cabanel, Centre National de Transfusion Sanguine, 75739 Paris, France
A. M. COUROUCE
Centre Edouard Rist, Paris
C. NARET C. CIANCIONNI S. DELONS
CARDIORESPIRATORY ARREST IN DIABETES
S:R,—We have similar
to
seen
cardiorespiratory arrest in a diabetic by Dr Page and Dr Watkins (Jan. 7,
that described
p. 14). A 49-year-old
male with a 20-year history of insulin-dependent diabetes mellitus presented with acute shortness of breath and diarrhoea. His supine blood-pressure was 150/80 mm Hg. Examination showed advanced diabetic retinopathy, postural hypotension, sinus tachycardia, bilateral rales, and extensive peripheral neuropathy. There was evidence of neurogenic bladder. Chest X-ray showed pulmonary oedema but no significant change in heart size. Blood-glucose was 160 mg/dl and serum-electrolytes were normal but there was hypoxia and hyper-
capnia.
,
While being treated, he suddenly stopped breathing. At that moment, the cardiac monitor showed sinus rhythm and the blood-pressure did not fall. Spontaneous respiration began again after several minutes of respiratory resuscitation. During his stay in the hospital, Holter monitoring did not show any rhythm disturbance. He had two more episodes of respiratory arrest during which cardiac function was unchanged but there was X-ray evidence of pulmonary cedema. 8 h of artificial ventilation were required after one of these episodes before spontaneous respiration returned. The patient left the hospital in a stable condition but a few weeks later was found dead in bed.
Rood, J. J. Lancet, 1977, ii,
1145. 2. Mathé, G., Schwartzenberg, L. Exp. Hæmat. 1976, 4, 256. 3. Williams, D. M., Lynch, R. E., Cartwright, G. E. Sem. Hemat. 1973, 10, 195. 4. Camitta, B. M., Thomas, E. D., Nathan, D. G., Santos, G., Gordon-Smith, E. C., Gale, R. P., Rappaport, J. M., Storb, R. Blood, 1976, 48, 63. 5. Camitta, B. M., Thomas, D., Nathan, D., Santos, G., Gordon-Smith, E., Rappaport, J. ibid. 1977, 48, suppl., p. 313.
1. Frösner, G.
G., Frösner, H.-R., Dienhardt, F., Haussman, W., Knabe, U. H. Lancet, 1977, ii, 1023. 2. Soulier, J. P., Couroucé-Pauty, A. M., Benamon-Djiane, D. Rev. fr. Transf.
1972, 15, 377. 3. Delons, S., and others. Proc. Eur. Dial. Transpl. Ass. 1974, 11, 237. 4. Couroucé-Pauty, A. M., Delons, S., Soulier, J. P. Am. J. med. Sci. 1975, 375. 5. Couroucé-Pauty, A. M., and others. Archs Malad. profess. (in the press).
270,
W. KING ENGEL RICHARD A. CUNEO HILTON B. LEVY
A.L.G. IN APLASTIC ANÆMIA
S!R,—The preliminary report by Speck et al. on the use of antilymphocyte globulin (A.L.G.) with or without partially compatible bone-marrow for treating severe aplastic anaemia is intriguing. However, as Speck et al. say, aplastic anaemia, even when severe, has a variable course. Thus, to assess the contribution of A.L.G. to survival, a control group treated identically except for A.L.G. is required. The controls and A.L.G. treated patients should be comparable in disease severity, interval from diagnosis to entry into study, and other factors, such as age, sex, and infection, that may affect survival. In the absence of concurrent controls, results of relatively small series may be misleading. For example, the trials of A.L.G. + incompatible marrow by Mathe et awl. were uncontrolled. Survival of 5/24 patients treated in this manner is no different than the survival of patients with severe aplastic anaemia receiving supportive care alone.3 Similarly, early uncontrolled reports of improved survival with androgen therapy for severe aplastic anaemia were not confirmed when these agents were evaluated in a controlled trial.4.5 Speck et al. recognise the limitations of their work. I hope that they will design follow-up trials to define the role of A.L.G. in treating severe aplastic anaemia. Department of Pediatrics, Midwest Children’s Cancer Center, Milwaukee Children’s Hospital, Milwaukee, Wisconsin 3233, U.S.A.
1.
Speck, B., Gluckman, E., Haak, H. L.,
BRUCE M. CAMITTA
van
ANTI-HBs IMMUNE GLOBULIN TO PREVENT HEPATITIS B
SiR,—Frosner et al.’ described three cases of hepatitis, after sexual contact or accidental needlestick exposure, despite administration of anti-HBs immune globulin (H.B.I.G.). They concluded that H.B.I.G. had not prevented hepatitis B but had merely extended the incubation period. We disagree with this conclusion, especially for the third case. If H.B.I.G. failed in the first two cases, it was probably because prophylaxis was attempted too late after exposure (12 days or more in the first case of sexual contact and 15 days in the second case). Such cases are not really failures of im-
munotherapy. In the third case, hepatitis B in a nurse 205 days after needlestick exposure, a second, undetected exposure 2-4 months after the detected incident is the more likely explanation. We have seen a similar case (hepatitis B 6 months after exposure and H.B.I.G.).3,4 This case was interpreted as a later, undetected contamination. The permanent exposure risk in haunodialysis units was the incentive for us to try repeated H.B.I.G. injections to achieve permanent protection.3,4 We have found that 5 ml H.B.LG., with the same activity as the international reference, protects for only 2 months5 despite weak levels of passive anti-HBs beyond this period. This residual anti-HBs is too weak to guarantee effective protection. In our experience H.B.I.G. prevents hepatitis B if the H.B.I.G. titre is at least as potent as the international reference, the dose is 0-08 ml/kg, the injection is given no more than 8 days after exposure, and the H.B.I.G. injections are repeated every 2 months if the risk of exposure is great and permanent. ’
Etablissement Cabanel, Centre National de Transfusion Sanguine, 75739 Paris, France
A. M. COUROUCE
Centre Edouard Rist, Paris
C. NARET C. CIANCIONNI S. DELONS
CARDIORESPIRATORY ARREST IN DIABETES
S:R,—We have similar
to
seen
cardiorespiratory arrest in a diabetic by Dr Page and Dr Watkins (Jan. 7,
that described
p. 14). A 49-year-old
male with a 20-year history of insulin-dependent diabetes mellitus presented with acute shortness of breath and diarrhoea. His supine blood-pressure was 150/80 mm Hg. Examination showed advanced diabetic retinopathy, postural hypotension, sinus tachycardia, bilateral rales, and extensive peripheral neuropathy. There was evidence of neurogenic bladder. Chest X-ray showed pulmonary oedema but no significant change in heart size. Blood-glucose was 160 mg/dl and serum-electrolytes were normal but there was hypoxia and hyper-
capnia.
,
While being treated, he suddenly stopped breathing. At that moment, the cardiac monitor showed sinus rhythm and the blood-pressure did not fall. Spontaneous respiration began again after several minutes of respiratory resuscitation. During his stay in the hospital, Holter monitoring did not show any rhythm disturbance. He had two more episodes of respiratory arrest during which cardiac function was unchanged but there was X-ray evidence of pulmonary cedema. 8 h of artificial ventilation were required after one of these episodes before spontaneous respiration returned. The patient left the hospital in a stable condition but a few weeks later was found dead in bed.
Rood, J. J. Lancet, 1977, ii,
1145. 2. Mathé, G., Schwartzenberg, L. Exp. Hæmat. 1976, 4, 256. 3. Williams, D. M., Lynch, R. E., Cartwright, G. E. Sem. Hemat. 1973, 10, 195. 4. Camitta, B. M., Thomas, E. D., Nathan, D. G., Santos, G., Gordon-Smith, E. C., Gale, R. P., Rappaport, J. M., Storb, R. Blood, 1976, 48, 63. 5. Camitta, B. M., Thomas, D., Nathan, D., Santos, G., Gordon-Smith, E., Rappaport, J. ibid. 1977, 48, suppl., p. 313.
1. Frösner, G.
G., Frösner, H.-R., Dienhardt, F., Haussman, W., Knabe, U. H. Lancet, 1977, ii, 1023. 2. Soulier, J. P., Couroucé-Pauty, A. M., Benamon-Djiane, D. Rev. fr. Transf.
1972, 15, 377. 3. Delons, S., and others. Proc. Eur. Dial. Transpl. Ass. 1974, 11, 237. 4. Couroucé-Pauty, A. M., Delons, S., Soulier, J. P. Am. J. med. Sci. 1975, 375. 5. Couroucé-Pauty, A. M., and others. Archs Malad. profess. (in the press).
270,
