- Email: [email protected]
POLYINOSINIC-POLYCYTIDYLIC ACID TREATMENT OF NEUROPATHY
503 the accurate diagnosis of small-bowel contamination in these patients and jejunal aspiration and culture with an open-ended tube is usually both simple and well tolerated. However, aspiration and culture of fasting gastric juice may suffice as an alternative as we have found that the results closely mirror those of small-bowel culture when the two examinations are
carried out concurrently. It seems that there are frequently abnormal numbers of bacteria in the upper small bowel in patients with a variety of general and gastrointestinal complaints and who are either old, have gastric achlorhydria, or have had peptic-ulcer surgery. However, the relationship of these bacteria to the clinical problem is conjectural and will be clarified only by further studies with accurate ieiunal bacteriolosv.
Gastrointestinal Centre, Southern General Hospital, Glasgow G514TF
R. J. HOLDEN P. MILLS L. CRAIG J. D. SLEIGH I. MACKENZIE W. WATSON G. WATKINSON G. P. CREAN
POST-THYROIDECTOMY THYROTOXICOSIS
SIR, The study reported by Dr Kalk and his colleagues (Feb. 11, p. 291) confirms previous reports that post-thyroidectomy recurrent hyperthyroidism occurs in varying but often large numbers of patients and re-emphasises the need for longterm surveillance in chronic disease, including late-onset recurrences or thyroid failure after treatment of hyperthyroidism.2.3 The studies Kalk et al. cite are of prevalence (not incidence), and are inevitably based on retrospective examination of survivors of those treated; the risk of recurrent hyperthyroidism will only be determined by measuring its incidence in longitudinal studies in defined patient groups. Such a plan for life-long follow-up, implemented in 1968,4 is now being evaluated by, for example, life-table techniques to estimate the cumulative probability of events such as recurrence and hypothyroidism after destructive therapy for hyperthyroidism. Kalk et al. refer to our studies5 on factors determining the long-term response to subtotal thyroidectomy but do not emphasise that environmental factors, such as dietary iodine and the variation in levels of autoimmune thyroiditis in different populations, may together be more important as determinants of recurrences than is remnant size alone. Comments on the relation between remnant size and outcome of surgery in different centres are probably meaningless unless they are accompanied by estimates of both the frequency and severity of thyroiditis in the gland and of the proportion of postoperative patients in whom the underlying disease remains active.6 Such activity may be identified by T3 suppression or T.R.H. stimulation tests (although there is disagreement about the comparability of the two techniques) and probably represent the only subgroup at risk of recurrent hyperthyroidism. Large remnants will never cause a recurrence in those patients in whom the extrapituitary stimulus to the gland has remitted and similarly a small remnant may not prevent it in those in whom the stimulus persists. Over one quarter of the Johannesburg patients were Black Africans in whom the frequency of autoimmune types of thy1.
Small,
w. r.
Lancet, 1967, i, 997.
2. Crooks, J. in Computers in the Service of Medicine (edited by G. McLachlan and R. A. Shegog) Nuffield Provincial Hospitals Trust, 1968. 3. Hedley, A. J., Fleming, C. J., Chesters, M. I., Michie, W., Crooks, J. Br.
med. J. 1970, i, 519. 4. Hedley, A. J., Scott, A. M., Debenham, G. Meth. Inf. Med. 1969, 8, 67. 5. Thjodleifsson, B., Hedley, A. J., Donald, D., Chesters, M. I., Kjeld, M., Beck, J. S., Crooks, J., Michie, W., Hall, R. Clin. Endocr. 1977, 7, 377. 6. Hedley, A. J., Ross, I. P., Beck, J. S., Donald, D., Albert-Recht, F., Michie, W., Crooks, J. Br. med. J. 1971, ii, 258.
roid disease seems low. 7-9Is the frequency of lasting remission after surgical treatment of hyperthyroidism different from that in Whiteq)
Department of Community Health, University Hospital and Medical School, Nottingham Department of Medicine, Gardiner Institute,
Western Infirmary,
A.
J. HEDLEY
Glasgow
R. E. YOUNG
Landspitalinn, Reykjavik, Iceland
B.
THJODLEIFSSON
POLYINOSINIC-POLYCYTIDYLIC ACID TREATMENT OF NEUROPATHY
SIR,--A patient with chronic relapsing polyneuropathy, probably dysimmune, has responded remarkably to treatment with polyinosinic-polycytidylic acid pOly-L-lysine stabilised with carboxymethyl cellulose (poly-l.c.L.C.). Poly-i.c.L.c. induces interferon in primates.’2 We have been using it in amyotrophic lateral sclerosis (A.L.S.) because of the possibility (unproved) that this disease has a chronic viral aetiology. While not of benefit in two A.L.S. patients (on no other therapy) treated weekly or twice weekly for 14 and 10 weeks at intravenous doses raised to 270 and 210 g/kg, respectively, the drug did elicit
an
influenza-like syndrome with infusion,
consisting of fever, chills, headache, and malaise for 4-12 h, and leucocyte changes (see below). S.G.P.T. frequently and S.G.O.T. very rarely were raised 2 1 1-1 fold for 3-5 days, but other laboratory tests, including liver function, serum-creatine-phosphokinase, and blood picture were unchanged. A 29-year-old man, known to us for 2 years, has had severe motor neuropathy of upper and lower limbs for 14 years. It had a subacute onset at age 15 and progressed over 3 months to wheelchair confinement, the patient being unable to feed himself. After 6 more months, some improvement began and continued for 11 years, initially in relation to 6-8 months of monthly corticotrophin treatment (A.C.T.H.). That improvement was slight; he could partially dress himself and walk with difficulty. The patient had two more severe exacerbations, at ages 26 and 28, one on no treatment and the other on prednisone 100 mg single-dose, alternate-day therapy, partial responses having followed A.C.T.H. given for 4 and 2 weeks. That last incomplete response then was treated partially but still unsatisfactorily with high single-dose daily prednisone for 8 at the end of which the third severe exacerbation occurred and was unresponsive to 9ymonths of azathioprine 3 mg/kg added to the prednisone dosage which had been reduced to 80 and 2.5 mg single doses on alternate days. Before the last two exacerbations motor conduction velocity was 34 m/s in the median nerve and 21 in the ulnar; cerebrospinal-fluid protein was 65 mg/dl, and with the last relapse it was 105. At that point the patient was very weak, unable to turn over in bed, stand alone, or walk (he used an electric wheelchair), or raise both arms to shoulder height. Because the patient improved temporarily during and for a few days after each influenza-like illness and because this apparently safe syndrome was provoked transiently by polyI.C.L.C. in our A.L.S. patients, we tried poly-I.c.L.c., 100 µg/kg by intravenous infusion over 30 min, once weekly, for 7 weeks to date. His prednisone remained unchanged at 80 and 2.5 mg on alternate days, and azathioprine was withdrawn. With each dose of poly-I.c.L.c. the patient had the usual transient ’flulike effects and transaminase changes noted above. 48 h after the first POlY-I.C.L.C. treatment the patient noted slight im-
months,
7. McGill, P. E. ibid. p. 679. 8. Gelfand, M. C. Afr. J. Medi. 1962, 8, 123. 9. Shee, J. C., Houston, W. ibid. 1963, 9, 267. 1. Levy, H. B., Baer, G., Barron, S., Buckler, C. E., Gibbs, C. J., Iadarola, M. J., London, W. T., Rice, J. J. infect. Dis. 1975, 132, 434. 2. Levine, A. S., Sivulich, M., Wiernick, P., Levy, H. B. Proc. Am. Ass. Cancer Res. (in the press).
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,
carried out concurrently. It seems that there are frequently abnormal numbers of bacteria in the upper small bowel in patients with a variety of general and gastrointestinal complaints and who are either old, have gastric achlorhydria, or have had peptic-ulcer surgery. However, the relationship of these bacteria to the clinical problem is conjectural and will be clarified only by further studies with accurate ieiunal bacteriolosv.
Gastrointestinal Centre, Southern General Hospital, Glasgow G514TF
R. J. HOLDEN P. MILLS L. CRAIG J. D. SLEIGH I. MACKENZIE W. WATSON G. WATKINSON G. P. CREAN
POST-THYROIDECTOMY THYROTOXICOSIS
SIR, The study reported by Dr Kalk and his colleagues (Feb. 11, p. 291) confirms previous reports that post-thyroidectomy recurrent hyperthyroidism occurs in varying but often large numbers of patients and re-emphasises the need for longterm surveillance in chronic disease, including late-onset recurrences or thyroid failure after treatment of hyperthyroidism.2.3 The studies Kalk et al. cite are of prevalence (not incidence), and are inevitably based on retrospective examination of survivors of those treated; the risk of recurrent hyperthyroidism will only be determined by measuring its incidence in longitudinal studies in defined patient groups. Such a plan for life-long follow-up, implemented in 1968,4 is now being evaluated by, for example, life-table techniques to estimate the cumulative probability of events such as recurrence and hypothyroidism after destructive therapy for hyperthyroidism. Kalk et al. refer to our studies5 on factors determining the long-term response to subtotal thyroidectomy but do not emphasise that environmental factors, such as dietary iodine and the variation in levels of autoimmune thyroiditis in different populations, may together be more important as determinants of recurrences than is remnant size alone. Comments on the relation between remnant size and outcome of surgery in different centres are probably meaningless unless they are accompanied by estimates of both the frequency and severity of thyroiditis in the gland and of the proportion of postoperative patients in whom the underlying disease remains active.6 Such activity may be identified by T3 suppression or T.R.H. stimulation tests (although there is disagreement about the comparability of the two techniques) and probably represent the only subgroup at risk of recurrent hyperthyroidism. Large remnants will never cause a recurrence in those patients in whom the extrapituitary stimulus to the gland has remitted and similarly a small remnant may not prevent it in those in whom the stimulus persists. Over one quarter of the Johannesburg patients were Black Africans in whom the frequency of autoimmune types of thy1.
Small,
w. r.
Lancet, 1967, i, 997.
2. Crooks, J. in Computers in the Service of Medicine (edited by G. McLachlan and R. A. Shegog) Nuffield Provincial Hospitals Trust, 1968. 3. Hedley, A. J., Fleming, C. J., Chesters, M. I., Michie, W., Crooks, J. Br.
med. J. 1970, i, 519. 4. Hedley, A. J., Scott, A. M., Debenham, G. Meth. Inf. Med. 1969, 8, 67. 5. Thjodleifsson, B., Hedley, A. J., Donald, D., Chesters, M. I., Kjeld, M., Beck, J. S., Crooks, J., Michie, W., Hall, R. Clin. Endocr. 1977, 7, 377. 6. Hedley, A. J., Ross, I. P., Beck, J. S., Donald, D., Albert-Recht, F., Michie, W., Crooks, J. Br. med. J. 1971, ii, 258.
roid disease seems low. 7-9Is the frequency of lasting remission after surgical treatment of hyperthyroidism different from that in Whiteq)
Department of Community Health, University Hospital and Medical School, Nottingham Department of Medicine, Gardiner Institute,
Western Infirmary,
A.
J. HEDLEY
Glasgow
R. E. YOUNG
Landspitalinn, Reykjavik, Iceland
B.
THJODLEIFSSON
POLYINOSINIC-POLYCYTIDYLIC ACID TREATMENT OF NEUROPATHY
SIR,--A patient with chronic relapsing polyneuropathy, probably dysimmune, has responded remarkably to treatment with polyinosinic-polycytidylic acid pOly-L-lysine stabilised with carboxymethyl cellulose (poly-l.c.L.C.). Poly-i.c.L.c. induces interferon in primates.’2 We have been using it in amyotrophic lateral sclerosis (A.L.S.) because of the possibility (unproved) that this disease has a chronic viral aetiology. While not of benefit in two A.L.S. patients (on no other therapy) treated weekly or twice weekly for 14 and 10 weeks at intravenous doses raised to 270 and 210 g/kg, respectively, the drug did elicit
an
influenza-like syndrome with infusion,
consisting of fever, chills, headache, and malaise for 4-12 h, and leucocyte changes (see below). S.G.P.T. frequently and S.G.O.T. very rarely were raised 2 1 1-1 fold for 3-5 days, but other laboratory tests, including liver function, serum-creatine-phosphokinase, and blood picture were unchanged. A 29-year-old man, known to us for 2 years, has had severe motor neuropathy of upper and lower limbs for 14 years. It had a subacute onset at age 15 and progressed over 3 months to wheelchair confinement, the patient being unable to feed himself. After 6 more months, some improvement began and continued for 11 years, initially in relation to 6-8 months of monthly corticotrophin treatment (A.C.T.H.). That improvement was slight; he could partially dress himself and walk with difficulty. The patient had two more severe exacerbations, at ages 26 and 28, one on no treatment and the other on prednisone 100 mg single-dose, alternate-day therapy, partial responses having followed A.C.T.H. given for 4 and 2 weeks. That last incomplete response then was treated partially but still unsatisfactorily with high single-dose daily prednisone for 8 at the end of which the third severe exacerbation occurred and was unresponsive to 9ymonths of azathioprine 3 mg/kg added to the prednisone dosage which had been reduced to 80 and 2.5 mg single doses on alternate days. Before the last two exacerbations motor conduction velocity was 34 m/s in the median nerve and 21 in the ulnar; cerebrospinal-fluid protein was 65 mg/dl, and with the last relapse it was 105. At that point the patient was very weak, unable to turn over in bed, stand alone, or walk (he used an electric wheelchair), or raise both arms to shoulder height. Because the patient improved temporarily during and for a few days after each influenza-like illness and because this apparently safe syndrome was provoked transiently by polyI.C.L.C. in our A.L.S. patients, we tried poly-I.c.L.c., 100 µg/kg by intravenous infusion over 30 min, once weekly, for 7 weeks to date. His prednisone remained unchanged at 80 and 2.5 mg on alternate days, and azathioprine was withdrawn. With each dose of poly-I.c.L.c. the patient had the usual transient ’flulike effects and transaminase changes noted above. 48 h after the first POlY-I.C.L.C. treatment the patient noted slight im-
months,
7. McGill, P. E. ibid. p. 679. 8. Gelfand, M. C. Afr. J. Medi. 1962, 8, 123. 9. Shee, J. C., Houston, W. ibid. 1963, 9, 267. 1. Levy, H. B., Baer, G., Barron, S., Buckler, C. E., Gibbs, C. J., Iadarola, M. J., London, W. T., Rice, J. J. infect. Dis. 1975, 132, 434. 2. Levine, A. S., Sivulich, M., Wiernick, P., Levy, H. B. Proc. Am. Ass. Cancer Res. (in the press).
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,