- Email: [email protected]
VIRUSES IN VIRAL HEPATITIS
778
incidence of
warts
and
lymphomas in patients
may be more than
immunosuppression
Medical Department C, Kommunehospitalet, 8000 Aarhus C, Denmark.
a
treated with chance association.
EDWIN S. SPENCER.
FASCIOLIASIS SIR,-In the past four months there have been 2 other small outbreaks of liver-fluke disease in man (each affecting five persons) in addition to the one mentioned in your annotation (March 29, p. 658). An important epidemiological point is that all the affected patients gave a history of eating wild, not cultivated, watercress. Fortunately, little wild watercress is gathered and less is sold. It is therefore understandable that fascioliasis in man appears in small outbreaks. There is no evidence that eating watercress cultivated under satisfactory conditions by established growers is likely to lead to illness. Watercress of unknown origin, and wild watercress, are potentially dangerous and should be avoided. Public Health
Laboratory, Dorchester, Dorset.
GEORGE TEE.
On the basis of these findings Dr. Glade and his colleagues cast doubt on the aetiological significance of E.B.v. in infectious mononucleosis (t.M.) and Burkitt’s lymphoma. We challenge their interpretation of these findings as they relate to l.M. In no instance did they show that their patients with- hepatitis lacked E.B.v. antigen in their leucocytes or E.B.v. antibodies in their serum before their illness, and no antibody rises were demonstrated. E.B.v. antibodies have been found to be consistently absent from the serum of patients before l.M. and regularly appear during the illness. Just as the finding of poliovirus antibodies does not signify a history of the paralytic disease, so the mere presence of E.B.v. antibodies in people with no known history of I.M. or Burkitt’s lymphoma bears no direct relation to questions of setiological association. As with many viruses, E.B.v. infections in childhood are likely to be unheralded events. It is certainly not surprising that heroin addicts were found to possess E.B.v. antibodies, but Dr. Glade and his colleagues do not mention whether or not their patients had past histories of l.M. Cultures of the type described have been derived with regularity from acute cases of l.M., and also from healthy individuals who possess E.B.v. antibodies, with or without a known history of I.M.2 This may represent persistence of the virus in leucocytes after l.M. or unrecognised E.B.v.
ADRENAL HÆMORRHAGE AFTER ABDOMINAL OPERATIONS SIR,ņThe fact that eight of the nine patients described by Dr. Fox (March 22, p. 600) died from adrenal haemorrhage following cancer surgery may suggest that this rare complication is particularly associated with malignant disease. Fatal adrenal haemorrhage sometimes occurs during pregnancy and can be associated with terminal haemorrhage from the lungs or elsewhere. The sudden onset of severe upper abdominal pain, localised below the costal margin or in the loin, associated with vomiting and collapse and aggravated by palpation of the enlarged pregnant uterus, can lead to the wrong diagnosis of uterine or adnexal complications. The possibility of a small adrenal haemorrhage being responsible for a similar but less acute syndrome should be considered. Division of Obstetrics and Gynæcology, Oxford. J. STALLWORTHY
VIRUSES IN VIRAL HEPATITIS
SIR,-Dr. Glade and his colleagues1 found " significant "
herpes-like virus (designated as the E.B.v., by others) in the serum of six heroin users and one child with acute viral hepatitis. E.B.v. antigen was demonstrated by immunofluorescence and/or electron-microscopy in the leucocytes of the three patients from whom continuous cell cultures were successfully established. antibody levels to Epstein-Barr virus,
1.
a
or
Glade, P. R., Hirshant, Y., Douglas, S. D., Hirschhorn, K. 1968, ii, 1273.
Lancet,
infection.
Although we have never denied the possibility that some stimulus " or agent(s) other than E.B.v. may play a role in the aetiology of l.M., we find it difficult to accept the hypothesis that E.B.v. is ubiquitous, its genome hiding in some cell awaiting the spark that might set it free to replicate and stimulate antibody production. Certainly all the available epidemiological and serological evidence is consonant with a rather straightforward and simple oetiological association between E.B.v. and I.M.3 Lest it be thought that the findings presented by Dr. Glade and his colleagues suggest a relation between E.B.v. and viral hepatitis, we wish to report that our own findings clearly point to a lack of any such relationship. Serial serum-specimens derived from carefully controlled human transmission studies of both short and long incubation-period types of viral hepatitis 4 have been tested for E.B.v. antibodies. Individuals without pre-existing E.B.v. antibodies developed none during the incubation period, illness, or recovery phase (up to 200 days after infection). If E.B.v. antibodies were present before hepatitis, no significant change in titre was demonstrable during the long follow-up period. Similar observations have been made in cases of naturally occurring hepatitis. In one instance (see accompanying table) E.B.v. antibodies, absent during hepatitis, appeared and rose to high titre during a later illness documented as l.M. on the basis of clinical, hsematological, and serological (heterophil) findings. If the E.B.v. genome had been present in this person as the result of some earlier undocumented infection, his episode of hepatitis failed to provide an appropriate stimulus for its release. We prefer to "
Diehl, V., Henle, G., Henle, W., Kohn, G. J. Virol. 1968, 2, 663. Evans, A. S., Niederman, J. C., McCollum, R. W. New Engl. J. Med. 1968, 279, 1121; ibid. 1969, 280, 112. 4. Krugman, S., Giles, J. P., Hammond, J. J. Am. med. Ass. 1967, 200, 365. 2. 3.
CLINICAL AND LABORATORY FINDINGS DURING EPISODES OF VIRAL HEPATITIS AND INFECTIOUS MONONUCLEOSIS IN THE SAMF PAT1RNT
779 believe that the i.M. encounter with E.B.v.
represented
the result of his initial
Department of Epidemiology, ROBERT W. MCCOLLUM and Public Health, JAMES C. NIEDERMAN Yale University School of Medicine, ALFRED S. EVANS. New Haven, Connecticut 06510. Department of Pediatrics, New York University School of Medicine, New York.
JOAN P. GILES.
MYOKYMIA WITH IMPAIRED MUSCULAR RELAXATION SIR,-The paper by Dr. Gardner-Medwin and Professor Walton (Jan. 18, p. 127) is of interest. Unfortunately instead of simplifying they further confuse the field of neuromuscular disease by, firstly, offering an unrealistic classification of myokymia, and, secondly, incorporating2 dubious cases into a well-described and clearcut syndrome. 1 In 1967 I published my third case of " continuous musclefibre activity ", and more recently have studied a 23-year-old These four cases, together woman with the same disease. with the cases of Mertens and ZschockeSigwald et al .,4 and Levy et al.,5 make this a specific disorder which I believe relates to an abnormal release of acetylcholine by the faulty presynaptic membrane. I have describedan increased sensitivity to curare which made me suspect that the postsynaptic membrane might also be at fault. The case described by Dr. Gardner-Medwin and Professor Walton belongs to this group, and I am informed by Dr. W. E. Wallis of the Cornell Institute, New York, that two cases are being investigated there at present. Many other patients with painful muscle spasms, myokymia, and hyperhidrosis, with and without myotonia, have been described, some responding to quinine, others to procainamide and diazepam. This hotch-potch of cases of diverse causes are of interest, as, for example, is case 1 of Greenhouse et al.and attempts to classify them will be made; but until more is known about the aetiology and the localisation of the abnormality such classification will remain
unsatisfactory. The syndrome of myoneural dysfunction which I described under the heading, A Syndrome of Continuous Muscle-fibre Activity, is a clearcut and well-localised syndrome. The syndrome was so named for the sake of clarity after prolonged consultation with the editor of the Journal of Neurology, Neurosurgery and Psychiatry. The most useful aspect of my paperwas that it described a disease for which I had found a cure, a point which has been overlooked by Dr. GardnerMedwin and Professor Walton. It is also unfortunate that not commented on the fascinating motor-nerveterminal work of Parisi and Raines,’ who described the production of a similar end-plate abnormality in cats and the protective action of phenytoin. The hyperhidrosis seen in the patients with continuous muscle-fibre activity correlates well with the raised metabolic rate. Myokymia is misleading as a label for this syndrome, for it does not explain the underlying tonic muscular activity, and the electromyogram (E.M.G.) findings are not like those of myokmyia. Richardson, who has jointly written a paper8 on myokymia, saw the E.M.G. tracings of my cases before publication and agreed that he had never seen anything of a similar nature. The motor-unit activity in " continuous musclefibre activity ", is continuous and haphazard; it is aggravated by voluntary activity, which is followed by a curious short
they have
1. 2.
3. 4. 5. 6.
7. 8.
Isaacs, H. J. Neurol. Neurosurg. Psychiat. 1961, 24, 319. Isaacs, H. ibid. 1967, 30, 126; S.Afr. J. Lab. clin. Med. 1964, 10, 93; Isaacs, H. Congress on Neurogenetics, Montreal, Canada, 1967 (in the press). Mertens, H. G., Zschocke, S. Klin. Wschr. 1965, 43, 917. Sigwald, J., Raverdy, P., Fardeau, M., Gremy, F., Mace De Lepinay, A., Bouttier, D., Danic, Revue Neurol. 1966, 155, 1003. Levy, J. A., Witting, E. Q., Ferraz, E. C. G. Archos Neuropsiquiat. Mexico, 1965, 23, 283. Greenhouse, A. H., Bicknell, J. M., Pesch, R. N., Weelinger, D. F. Neurology, Minneap. 1967, 17, 263. Parisi, A. F., Raines, A. Fedn. Proc. 1963, 22, 390 (abstract). Harman, J. B., Richardson, A. T. Lancet, 1954, ii, 473.
of E.M.G. silence. Myokymia as a label is wrong, too, because the activity does, not wax and wane, and the E.M.G. bears no similarity. Impaired muscular relaxation is also an incorrect term, for the muscle in fact relaxes normally once the stimulus to continue contraction is removed, as can be shown by the response to therapy and the response to direct muscle stimulation during depolarisation block. Until a more helpful label is found, I feel that it would be reasonable to continue to refer to this interesting and highly characteristic myoneural defect as a syndrome of continuous muscle-fibre activity. HYAM ISAACS. Johannesburg.
period
HOSPITAL AIR SiR,ņThe grudging tone of your leading article (March 29, p. 655) by no means does justice to the potentialities of the laminar-flow system of ventilation in medicine. This method is already in use in the care of leukamlic patients, but such a " special care " unit and the operatingroom represent only a fraction of the medical micro-environments in which it could be usefully deployed. The burns unit, the premature-baby unit, the labour suite, the blood-transfusion laboratory, and the bacteriology and virus laboratories, readily spring to mind in this connection. As far as the operating-room is concerned, an analogy with the advent of the antiseptic spray is by no means farfetched, for it has already been found possible, using the most makeshift apparatus, to produce an abacterial environment at the site of the incision during routine surgical procedures.I Nor would it appear to be necessary to rebuild the operating-room to obtain such a contamination-free environment, though a purpose-built room would be the ideal solution. The experience of the electronic industry has shown that a vertical laminar-flow enclosure within the existing operatingroom, using the heated and humidified air already supplied, is a practicable and cheap substitute. Such a unit has been designed, and for a sum of E2000-3000 could convert any operating-room, however decrepit, into the equivalent of a 100 class clean room on the U.S.A. Federal Standard 209a with environmental air free of all particles larger than 4 -. In microbiological terms this means bacteria-free, for Noble et al. have shown that bacteria rarely exist in the air as single unattached cells but ride on particles of dust or skin-scales of a minimum size of 4 (j<.. Unfortunately the imaginative " leap in the dark " which is a necessary preliminary to supporting such a project has not been taken, and the project remains a theoretical concept. Bacteriology Department, C. C. SCOTT. University of Dundee. rather
SYMPATHETIC OVERACTIVITY IN TETANUS SIR,-Dr. Prys-Roberts and his colleagues (March 15, p. 542) are correct in their assumption that the swinging bloodpressure found in some cases of severe tetanus is due to sympathetic overactivity. Using a semiautomated method for the differential determination of plasma-catecholamines,8 workers for this unit have demonstrated rises in circulating adrenaline and noradrenaline in three such patients.4 Even greater and more prolonged elevations in catecholamine levels have been found in another patient with marked fluctuations in blood-pressure. All four patients were curarised and ventilated with normal oxygen and carbon-dioxide tensions, and all received large doses of chlorpromazine. We have failed to demonstrate an increase in either adrenaline or noradrenaline in one case of severe tetanus without cardiovascular upset. 1. 2.
Goodrich, E. O. Contam. Cont. J. September, 1966. Noble, W. C., Lidwell, O. M., Kingston, D. J. Hyg. Camb. 1963, 61,
385. 3. McCullough, H. J. clin. Path. 1968, 4. Keilty, S. R., Gray, R. C., Dundee, 1968, ii, 195.
21, 759. J. W., McCullough, H. Lancet,
incidence of
warts
and
lymphomas in patients
may be more than
immunosuppression
Medical Department C, Kommunehospitalet, 8000 Aarhus C, Denmark.
a
treated with chance association.
EDWIN S. SPENCER.
FASCIOLIASIS SIR,-In the past four months there have been 2 other small outbreaks of liver-fluke disease in man (each affecting five persons) in addition to the one mentioned in your annotation (March 29, p. 658). An important epidemiological point is that all the affected patients gave a history of eating wild, not cultivated, watercress. Fortunately, little wild watercress is gathered and less is sold. It is therefore understandable that fascioliasis in man appears in small outbreaks. There is no evidence that eating watercress cultivated under satisfactory conditions by established growers is likely to lead to illness. Watercress of unknown origin, and wild watercress, are potentially dangerous and should be avoided. Public Health
Laboratory, Dorchester, Dorset.
GEORGE TEE.
On the basis of these findings Dr. Glade and his colleagues cast doubt on the aetiological significance of E.B.v. in infectious mononucleosis (t.M.) and Burkitt’s lymphoma. We challenge their interpretation of these findings as they relate to l.M. In no instance did they show that their patients with- hepatitis lacked E.B.v. antigen in their leucocytes or E.B.v. antibodies in their serum before their illness, and no antibody rises were demonstrated. E.B.v. antibodies have been found to be consistently absent from the serum of patients before l.M. and regularly appear during the illness. Just as the finding of poliovirus antibodies does not signify a history of the paralytic disease, so the mere presence of E.B.v. antibodies in people with no known history of I.M. or Burkitt’s lymphoma bears no direct relation to questions of setiological association. As with many viruses, E.B.v. infections in childhood are likely to be unheralded events. It is certainly not surprising that heroin addicts were found to possess E.B.v. antibodies, but Dr. Glade and his colleagues do not mention whether or not their patients had past histories of l.M. Cultures of the type described have been derived with regularity from acute cases of l.M., and also from healthy individuals who possess E.B.v. antibodies, with or without a known history of I.M.2 This may represent persistence of the virus in leucocytes after l.M. or unrecognised E.B.v.
ADRENAL HÆMORRHAGE AFTER ABDOMINAL OPERATIONS SIR,ņThe fact that eight of the nine patients described by Dr. Fox (March 22, p. 600) died from adrenal haemorrhage following cancer surgery may suggest that this rare complication is particularly associated with malignant disease. Fatal adrenal haemorrhage sometimes occurs during pregnancy and can be associated with terminal haemorrhage from the lungs or elsewhere. The sudden onset of severe upper abdominal pain, localised below the costal margin or in the loin, associated with vomiting and collapse and aggravated by palpation of the enlarged pregnant uterus, can lead to the wrong diagnosis of uterine or adnexal complications. The possibility of a small adrenal haemorrhage being responsible for a similar but less acute syndrome should be considered. Division of Obstetrics and Gynæcology, Oxford. J. STALLWORTHY
VIRUSES IN VIRAL HEPATITIS
SIR,-Dr. Glade and his colleagues1 found " significant "
herpes-like virus (designated as the E.B.v., by others) in the serum of six heroin users and one child with acute viral hepatitis. E.B.v. antigen was demonstrated by immunofluorescence and/or electron-microscopy in the leucocytes of the three patients from whom continuous cell cultures were successfully established. antibody levels to Epstein-Barr virus,
1.
a
or
Glade, P. R., Hirshant, Y., Douglas, S. D., Hirschhorn, K. 1968, ii, 1273.
Lancet,
infection.
Although we have never denied the possibility that some stimulus " or agent(s) other than E.B.v. may play a role in the aetiology of l.M., we find it difficult to accept the hypothesis that E.B.v. is ubiquitous, its genome hiding in some cell awaiting the spark that might set it free to replicate and stimulate antibody production. Certainly all the available epidemiological and serological evidence is consonant with a rather straightforward and simple oetiological association between E.B.v. and I.M.3 Lest it be thought that the findings presented by Dr. Glade and his colleagues suggest a relation between E.B.v. and viral hepatitis, we wish to report that our own findings clearly point to a lack of any such relationship. Serial serum-specimens derived from carefully controlled human transmission studies of both short and long incubation-period types of viral hepatitis 4 have been tested for E.B.v. antibodies. Individuals without pre-existing E.B.v. antibodies developed none during the incubation period, illness, or recovery phase (up to 200 days after infection). If E.B.v. antibodies were present before hepatitis, no significant change in titre was demonstrable during the long follow-up period. Similar observations have been made in cases of naturally occurring hepatitis. In one instance (see accompanying table) E.B.v. antibodies, absent during hepatitis, appeared and rose to high titre during a later illness documented as l.M. on the basis of clinical, hsematological, and serological (heterophil) findings. If the E.B.v. genome had been present in this person as the result of some earlier undocumented infection, his episode of hepatitis failed to provide an appropriate stimulus for its release. We prefer to "
Diehl, V., Henle, G., Henle, W., Kohn, G. J. Virol. 1968, 2, 663. Evans, A. S., Niederman, J. C., McCollum, R. W. New Engl. J. Med. 1968, 279, 1121; ibid. 1969, 280, 112. 4. Krugman, S., Giles, J. P., Hammond, J. J. Am. med. Ass. 1967, 200, 365. 2. 3.
CLINICAL AND LABORATORY FINDINGS DURING EPISODES OF VIRAL HEPATITIS AND INFECTIOUS MONONUCLEOSIS IN THE SAMF PAT1RNT
779 believe that the i.M. encounter with E.B.v.
represented
the result of his initial
Department of Epidemiology, ROBERT W. MCCOLLUM and Public Health, JAMES C. NIEDERMAN Yale University School of Medicine, ALFRED S. EVANS. New Haven, Connecticut 06510. Department of Pediatrics, New York University School of Medicine, New York.
JOAN P. GILES.
MYOKYMIA WITH IMPAIRED MUSCULAR RELAXATION SIR,-The paper by Dr. Gardner-Medwin and Professor Walton (Jan. 18, p. 127) is of interest. Unfortunately instead of simplifying they further confuse the field of neuromuscular disease by, firstly, offering an unrealistic classification of myokymia, and, secondly, incorporating2 dubious cases into a well-described and clearcut syndrome. 1 In 1967 I published my third case of " continuous musclefibre activity ", and more recently have studied a 23-year-old These four cases, together woman with the same disease. with the cases of Mertens and ZschockeSigwald et al .,4 and Levy et al.,5 make this a specific disorder which I believe relates to an abnormal release of acetylcholine by the faulty presynaptic membrane. I have describedan increased sensitivity to curare which made me suspect that the postsynaptic membrane might also be at fault. The case described by Dr. Gardner-Medwin and Professor Walton belongs to this group, and I am informed by Dr. W. E. Wallis of the Cornell Institute, New York, that two cases are being investigated there at present. Many other patients with painful muscle spasms, myokymia, and hyperhidrosis, with and without myotonia, have been described, some responding to quinine, others to procainamide and diazepam. This hotch-potch of cases of diverse causes are of interest, as, for example, is case 1 of Greenhouse et al.and attempts to classify them will be made; but until more is known about the aetiology and the localisation of the abnormality such classification will remain
unsatisfactory. The syndrome of myoneural dysfunction which I described under the heading, A Syndrome of Continuous Muscle-fibre Activity, is a clearcut and well-localised syndrome. The syndrome was so named for the sake of clarity after prolonged consultation with the editor of the Journal of Neurology, Neurosurgery and Psychiatry. The most useful aspect of my paperwas that it described a disease for which I had found a cure, a point which has been overlooked by Dr. GardnerMedwin and Professor Walton. It is also unfortunate that not commented on the fascinating motor-nerveterminal work of Parisi and Raines,’ who described the production of a similar end-plate abnormality in cats and the protective action of phenytoin. The hyperhidrosis seen in the patients with continuous muscle-fibre activity correlates well with the raised metabolic rate. Myokymia is misleading as a label for this syndrome, for it does not explain the underlying tonic muscular activity, and the electromyogram (E.M.G.) findings are not like those of myokmyia. Richardson, who has jointly written a paper8 on myokymia, saw the E.M.G. tracings of my cases before publication and agreed that he had never seen anything of a similar nature. The motor-unit activity in " continuous musclefibre activity ", is continuous and haphazard; it is aggravated by voluntary activity, which is followed by a curious short
they have
1. 2.
3. 4. 5. 6.
7. 8.
Isaacs, H. J. Neurol. Neurosurg. Psychiat. 1961, 24, 319. Isaacs, H. ibid. 1967, 30, 126; S.Afr. J. Lab. clin. Med. 1964, 10, 93; Isaacs, H. Congress on Neurogenetics, Montreal, Canada, 1967 (in the press). Mertens, H. G., Zschocke, S. Klin. Wschr. 1965, 43, 917. Sigwald, J., Raverdy, P., Fardeau, M., Gremy, F., Mace De Lepinay, A., Bouttier, D., Danic, Revue Neurol. 1966, 155, 1003. Levy, J. A., Witting, E. Q., Ferraz, E. C. G. Archos Neuropsiquiat. Mexico, 1965, 23, 283. Greenhouse, A. H., Bicknell, J. M., Pesch, R. N., Weelinger, D. F. Neurology, Minneap. 1967, 17, 263. Parisi, A. F., Raines, A. Fedn. Proc. 1963, 22, 390 (abstract). Harman, J. B., Richardson, A. T. Lancet, 1954, ii, 473.
of E.M.G. silence. Myokymia as a label is wrong, too, because the activity does, not wax and wane, and the E.M.G. bears no similarity. Impaired muscular relaxation is also an incorrect term, for the muscle in fact relaxes normally once the stimulus to continue contraction is removed, as can be shown by the response to therapy and the response to direct muscle stimulation during depolarisation block. Until a more helpful label is found, I feel that it would be reasonable to continue to refer to this interesting and highly characteristic myoneural defect as a syndrome of continuous muscle-fibre activity. HYAM ISAACS. Johannesburg.
period
HOSPITAL AIR SiR,ņThe grudging tone of your leading article (March 29, p. 655) by no means does justice to the potentialities of the laminar-flow system of ventilation in medicine. This method is already in use in the care of leukamlic patients, but such a " special care " unit and the operatingroom represent only a fraction of the medical micro-environments in which it could be usefully deployed. The burns unit, the premature-baby unit, the labour suite, the blood-transfusion laboratory, and the bacteriology and virus laboratories, readily spring to mind in this connection. As far as the operating-room is concerned, an analogy with the advent of the antiseptic spray is by no means farfetched, for it has already been found possible, using the most makeshift apparatus, to produce an abacterial environment at the site of the incision during routine surgical procedures.I Nor would it appear to be necessary to rebuild the operating-room to obtain such a contamination-free environment, though a purpose-built room would be the ideal solution. The experience of the electronic industry has shown that a vertical laminar-flow enclosure within the existing operatingroom, using the heated and humidified air already supplied, is a practicable and cheap substitute. Such a unit has been designed, and for a sum of E2000-3000 could convert any operating-room, however decrepit, into the equivalent of a 100 class clean room on the U.S.A. Federal Standard 209a with environmental air free of all particles larger than 4 -. In microbiological terms this means bacteria-free, for Noble et al. have shown that bacteria rarely exist in the air as single unattached cells but ride on particles of dust or skin-scales of a minimum size of 4 (j<.. Unfortunately the imaginative " leap in the dark " which is a necessary preliminary to supporting such a project has not been taken, and the project remains a theoretical concept. Bacteriology Department, C. C. SCOTT. University of Dundee. rather
SYMPATHETIC OVERACTIVITY IN TETANUS SIR,-Dr. Prys-Roberts and his colleagues (March 15, p. 542) are correct in their assumption that the swinging bloodpressure found in some cases of severe tetanus is due to sympathetic overactivity. Using a semiautomated method for the differential determination of plasma-catecholamines,8 workers for this unit have demonstrated rises in circulating adrenaline and noradrenaline in three such patients.4 Even greater and more prolonged elevations in catecholamine levels have been found in another patient with marked fluctuations in blood-pressure. All four patients were curarised and ventilated with normal oxygen and carbon-dioxide tensions, and all received large doses of chlorpromazine. We have failed to demonstrate an increase in either adrenaline or noradrenaline in one case of severe tetanus without cardiovascular upset. 1. 2.
Goodrich, E. O. Contam. Cont. J. September, 1966. Noble, W. C., Lidwell, O. M., Kingston, D. J. Hyg. Camb. 1963, 61,
385. 3. McCullough, H. J. clin. Path. 1968, 4. Keilty, S. R., Gray, R. C., Dundee, 1968, ii, 195.
21, 759. J. W., McCullough, H. Lancet,