172 with IgG heteroantibody (chicken EA) on the P.B.L. from 14 patients with myasthenia gravis, 8 of whom had undergone thymectomy 1-8 years ago. The techniques have been described.8,10 The results, together with tests on P.B.L. of 25 normal subjects of similar age and sex distribution to the myasthenic patients, are shown in table I. Although a minority of tests were performed with 0-5% suspensions of auto-E, which we have since shown to be below the optimum concentration, the percentages of A.R.F.C. in all three groups are many times greater than those reported in man by Dr Charreire and Dr Bach, almost certainly because of differences in technique. We have regarded as A.R.F.C. those lymphocytes binding 3 or more auto-E: if lymphocytes binding 1 or 2 auto-E are included, the total approximates to 10% of the P.B.L. The mean percentages of A.R.F.C. were not significantly different for the three groups, nor does consideration of the mean total lymphocyte counts (not shown) suggest a significant rise in the absolute numbers of A.R.F.C. following thymectomy. We have also compared the percentages of A.R.F.C. in the P.B.L. of normal subjects of different age-groups, using
TABLE II-PERCENTAGES OF AUTOROSETTE-FORMING LYMPHOCYTES AT DIFFERENT AGES
optimum (1-5%) suspensions of auto-E, and have observed no significant differences between the ages of 18 and 55 years (table 11). These results provide no evidence that thymectomy or ageing are associated with an increase of A.R.F.C. in the P.B.L. We suspect that autorosette formation by P.B.L. may be of little immunological significance, partly because we have observed rosette formation by similar small percentages of human P.B.L. using erythrocytes of various species (guineapig, mouse, rat, and chicken E), and partly because human P.B.L. in culture are apparently not stimulated to transformation by human E.11 Lastly, we are unaware of reports on the proportions of T and B human P.B.L. following thymectomy. Accepting the sheep-E and chicken-EA rosette tests as indications of T and B cells, respectively, our results suggest that there has been no significant fall in the T-cell population up to 8 Care was taken, at years after thymectomy (table I). operation, to remove the anterior mediastinal fatty tissue, and it seems likely that thymectomy was complete or nearly so, in which case maintenance of the T-cell population in these patients appears to be largely independent of the thymus. It is not known, however, whether they are capable of normal immune responses to previously unencountered
antigens.
We thank Mr K. Fraser, who performed the for permission to report these findings.
Glasgow University Department of Pathology, Western Infirmary, Glasgow. Glasgow University Department of Neurology, Institute of Neurological Science, Southern General Hospital,
Glasgow.
thymectomies,
G. P. SANDILANDS KATHLEEN GRAY ANNE COONEY J. R. ANDERSON.
J. A. SIMPSON P. O. BEHAN.
HALOPHILIC NON-CHOLERA VIBRIO INFECTIONS
SIR,-We read with interest, but with some misgivings, account by Dr Thorsteinsson and others (Nov. 30, p. 1283) of the clinical manifestations in three cases of systemic infection with halophilic non-cholera vibrios. We agree that, whether halophilic or not, non-cholera vibrios (N.c.v.) as a group are as yet poorly defined. It is therefore unfortunate that no information is given about the bacteriological tests used for identification of the organisms isolated. For the same reason, it is important that misleading statements should not be made. Thus, the micro-aerophilic organism previously called Vibrio fetus is so different from vibrios that it is now classified in the genus Camplyobacter. Although of considerable veterinary importance, this organism is hardly a wellknown cause of systemic infection in man. The suggestion that gram-films of faeces are useful in revealing distinctive curved rods when diarrhoea caused by N.c.v. is suspectedon whatever grounds-is as unsound as the suggestion that such gram-negative rods seen in smears from infected the
tissues could indicate the presence of N.c.v. A search for curved rods in clinical specimens plays no part in the diagnosis of any infection with vibrios. This can be established only by isolation of the causal organism. If infection with vibrios of any kind is suspected-indeed even if not suspected in patients with recent diarrhoeal disease-it would be more appropriate to use a culture medium such as T.c.B.s. (thiosulphate citrate bile-salt sucrose agar) selective for vibrios in addition to routine procedures. Since some marine vibrios will not grow if the salt concentration is greater than 6-8%, any classification into halophilic and non-halophilic species on the basis of their salt tolerance would be more understandable if the ability to grow without added salt was used as a criterion. Finally, the statement that halophilic vibrios survive short exposure to near-boiling temperatures misinterprets the paper cited. This referred to outbreaks of V. parahaemolyticus food-poisoning which were attributed to inadequate cooking and/or incorrect handling of seafoods. It should be made clear that vibrios are in fact fully sensitive to heat. Public Health Laboratory, Royal Cornwall Hospital (City), Truro TR1 2HZ.
Public Health Laboratory, Preston Hall, Maidstone ME20 7NH.
11.
Sandilands, G., Gray, K., Cooney, A., Browning, J. D., Grant, R. M., Anderson, J. R., Dagg, J. H., Lucie, N. Lancet, 1974, i, 903. Hardy, D. A., Ling, N. R. Nature, 1969, 121, 545.
A. L. FURNISS.
SiR,—The interesting article by Dr Thorsteinsson and a significant error in including the organism formerly referred to as Vibrio fetus among the non-halophilic non-cholera vibrios. Although the latter organism shares the " comma shape of the prototype of the genus Vibrio (V. co/gr), most authorities would now agree that biochemically it is quite dissimilar. Hence, this organism has been regrouped into an entirely separate genus and is properly referred to as Campylobacter fetus.l2 The genus Campylobacter is a member of the family Spirillacea, which includes the genus Spirillum as well as Campylobacter. In contrast, the genus Vibrio is properly a member of the family Vibrionacetv which also includes the genuses Aeromonas Pleisomonas, Photobacterium, and Lucibacterium. All members of the genus Campylobacter are motile, flagellated, microaerophilic, gram-negative organisms. Four subtypes have, to date, been isolated from human sources. others did contain
"
1.
10.
G. I. BARROW.
2.
Buchanan, R. E., Gibbons, N. E. (editors) Bergey’s Manual of Determinative Bacteriology. Baltimore, 1974. Lennette, E. H., Spaulding, E. H., Truant, J. P. (editors). Manual of Clinical Microbiology. American Society for Microbiology, Washington, D.C., 1974.
173
Campylobacter fetus var. fetus has been associated with gastroenteritis, endocarditis, and bacteraemia in man; Campylobacter fetus var. intestinalis, Campylobacter fetus var. jejuni, and Campylobacter sputorum var. sputorum clinical isolates. Of these four the first is clearly established as a human species, only pathogen; the others appear to be predominantly animal pathogens or saprophytic members of the normal human flora which may be pathogenic for man under unusual circumstances. Other members of the genus Campylobacter have also been described whose precise taxonomic position and role in human disease remain unclear. Although confusion has been inevitable in the past because of the poorly defined status and questionable pathogenicity of many of these organisms, it is nonetheless obligatory at this point for both clinicians and microbiologists to adhere to what is now standard taxonomy and nomenclature in referring to these organisms in the literature.
are
the other
adenovirus and herpesvirus infections. Also one single application was effective in the prevention of infection after removal of foreign bodies and after ophthalmic surgery. Moscow Helmholtz
Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, U.S.A.
MICHAEL L. TAPPER.
SOLUBLE OPHTHALMIC DRUG INSERTS SIR,-An experimental and clinical study has been completed on a better way of introducing medication into the eye. Experiments demonstrated the potential of new films (inserts) polyvinylalcohol medicinal ophthalmic mpregnated with antibiotics.1 Yet it was observed 2,
Ophthalmological
Institute, Moscow, U.S.S.R.
common
Y. F. MAICHUK.*
INTRAVENOUS PROSTAGLANDINS AND OXYTOCIN FOR MID-TRIMESTER ABORTION
SIR,-Opinions still vary as to the most effective way of terminating mid-trimester pregnancies, although most clinicians now favour prostaglandins. We report the successful termination of 19 consecutive late first and second trimester pregnancies using a combination of intravenous prostaglandins E2 (P.G.E.2 Upjohn) and
oxytocin (’ Syntocinon’). P.G.E.:(5 mg. in 500 ml. of 5% glucose) was infused into a superficial arm vein at an initial rate of 2-5 (.Lg. per minute, the rate being increased to 5 ;jLg. per minute after half an hour. If after four hours the uterine response was regarded as inadequate
the P.G.E.. infusion was increased to a maximum of 10 jj.g. per minute. To allow ample time for the enhancement phenomenon,’,2 INDUCTION OF ABORTION BY A COMBINATION OF INTRAVENOUS P.G.E.. AND OXYTOCIN
that they, like polypeptide-polysaccharide ocular inserts,33 did not dissolve in the conjunctival sac, and discomfort necessitated their removal from the sac. Therefore soluble ophthalmic drug inserts (S.O.D.I.) have been suggested2 and produced by the Moscow Helmholtz Ophthalmological Institute in collaboration with the All-Union Research Institute for Medical Equipment, U.S.S.R. S.O.D.I. were endorsed for use in ophthalmic practice in the U.S.S.R., following the June 11,1971, decision of the Pharmacological Committee, Ministry of Health. S.O.D.1. are made from polymers of polyacrylamide, ethylacrylate, and vinylpyrrolidone, prepared as thin elastic oval plates with neomycin, kanamycin, sulphamethoxypyrid-
azine, idoxuridine,Florenal ’, atropine, pilocarpine, dexamethasone, and other drugs used in ophthalmology. S.O.D.I. offer a number of advantages over eye-drops (aqueous solutions, viscous solutions of polymers, suspensions), ointments, and subconjunctival injections. In fact, their use makes it possible to achieve prolonged
bioavailability of active substances in the conjunctival fluid and conjunctival and corneal tissue. Though in many of the applications studied S.O.D.I. dissolved in 60-90 minutes, the incorporated active material was found in the conjunctival fluid for up to 34-72 hours. This long duration secures therapeutic concentrations in the conjunctival sac, enhances the penetration of drugs into the tissues and may therefore replace subconjunctival injections in certain cases. This possibility has, of course, to be weighed against tolerance of the active material. However, experience with more than 500 patients (a single application daily or every other day for a maximum of 10 days) demonstrated good tolerance and therapeutic efficacy in different forms of glaucoma, keratitis, iridocyclitis, cornea ulceration, trachoma, conjunctivitis, and 1. 2.
Maichuk, Maichuk,
Y. F. Antibiotiki, 1967, 5, 435. Y. F. in Proceedings of Moscow
Ophthalmological
Conference, 1967, p. 403. 3. Dohlman, C. H., Pavan-Langston, Dr., Rose, J. Ann. Ophthalmol. 1972, 4, 823. 4. Maichuk, Y. F., Khromov, G. L., Koneva, E. B., Tishina, I. F., Pozdnijkov, V. I. in Proceedings of Conference on Ophthalmology, Chuvash, A.S.S.R., 1970, p. 136.
+ = 1 or 2 episodes of vomiting. + + 3 or 4 episodes of vomiting. + + + =more than 4 episodes of vomiting. =
c=complete.
oxytocin
i/c=incomplete.
started two hours after the P.G.E’2 and infused at a of 128 mu per minute. Mixing the P.G.E., and in the same bottle of 5 % glucose had no adverse effects. was
constant rate
oxytocin
Individual results are shown in the accompanying table. The mean total dose of P.G.E’2 used was 5-9 mg.- at an overall rate of 6-1 g. per minute. The average induction/ delivery interval was 16 hours, with only 1 patient (13) taking more than 24 hours. In 13 cases (68%) abortion was
complete. 13 women experienced vomiting, but the nursing staff said that this was distressing in only 2 cases, the remainder responding well to ’Stemetil’ by intramuscular injection. Pain was not a problem and was well controlled by pethidine, the average dose of which was 100 mg.
When the two uterine stimulatants
were run
through the same infusion set, there was a tendency to superficial thrombophlebitis, but this was never anything *
Present address: Regional Adviser, W.H.O., E.M.R.O., P.O., Box 1517, Alexandria, Arab Republic of Egypt.
1. 2.
Brummer, H. C. J. Obstet. Gynœc. Br. Commonw. 1971, 78, 305. Gillespie, A. Br. med. J. 1972, i : 150.
TABLE II-PERCENTAGES OF AUTOROSETTE-FORMING LYMPHOCYTES AT DIFFERENT AGES
optimum (1-5%) suspensions of auto-E, and have observed no significant differences between the ages of 18 and 55 years (table 11). These results provide no evidence that thymectomy or ageing are associated with an increase of A.R.F.C. in the P.B.L. We suspect that autorosette formation by P.B.L. may be of little immunological significance, partly because we have observed rosette formation by similar small percentages of human P.B.L. using erythrocytes of various species (guineapig, mouse, rat, and chicken E), and partly because human P.B.L. in culture are apparently not stimulated to transformation by human E.11 Lastly, we are unaware of reports on the proportions of T and B human P.B.L. following thymectomy. Accepting the sheep-E and chicken-EA rosette tests as indications of T and B cells, respectively, our results suggest that there has been no significant fall in the T-cell population up to 8 Care was taken, at years after thymectomy (table I). operation, to remove the anterior mediastinal fatty tissue, and it seems likely that thymectomy was complete or nearly so, in which case maintenance of the T-cell population in these patients appears to be largely independent of the thymus. It is not known, however, whether they are capable of normal immune responses to previously unencountered
antigens.
We thank Mr K. Fraser, who performed the for permission to report these findings.
Glasgow University Department of Pathology, Western Infirmary, Glasgow. Glasgow University Department of Neurology, Institute of Neurological Science, Southern General Hospital,
Glasgow.
thymectomies,
G. P. SANDILANDS KATHLEEN GRAY ANNE COONEY J. R. ANDERSON.
J. A. SIMPSON P. O. BEHAN.
HALOPHILIC NON-CHOLERA VIBRIO INFECTIONS
SIR,-We read with interest, but with some misgivings, account by Dr Thorsteinsson and others (Nov. 30, p. 1283) of the clinical manifestations in three cases of systemic infection with halophilic non-cholera vibrios. We agree that, whether halophilic or not, non-cholera vibrios (N.c.v.) as a group are as yet poorly defined. It is therefore unfortunate that no information is given about the bacteriological tests used for identification of the organisms isolated. For the same reason, it is important that misleading statements should not be made. Thus, the micro-aerophilic organism previously called Vibrio fetus is so different from vibrios that it is now classified in the genus Camplyobacter. Although of considerable veterinary importance, this organism is hardly a wellknown cause of systemic infection in man. The suggestion that gram-films of faeces are useful in revealing distinctive curved rods when diarrhoea caused by N.c.v. is suspectedon whatever grounds-is as unsound as the suggestion that such gram-negative rods seen in smears from infected the
tissues could indicate the presence of N.c.v. A search for curved rods in clinical specimens plays no part in the diagnosis of any infection with vibrios. This can be established only by isolation of the causal organism. If infection with vibrios of any kind is suspected-indeed even if not suspected in patients with recent diarrhoeal disease-it would be more appropriate to use a culture medium such as T.c.B.s. (thiosulphate citrate bile-salt sucrose agar) selective for vibrios in addition to routine procedures. Since some marine vibrios will not grow if the salt concentration is greater than 6-8%, any classification into halophilic and non-halophilic species on the basis of their salt tolerance would be more understandable if the ability to grow without added salt was used as a criterion. Finally, the statement that halophilic vibrios survive short exposure to near-boiling temperatures misinterprets the paper cited. This referred to outbreaks of V. parahaemolyticus food-poisoning which were attributed to inadequate cooking and/or incorrect handling of seafoods. It should be made clear that vibrios are in fact fully sensitive to heat. Public Health Laboratory, Royal Cornwall Hospital (City), Truro TR1 2HZ.
Public Health Laboratory, Preston Hall, Maidstone ME20 7NH.
11.
Sandilands, G., Gray, K., Cooney, A., Browning, J. D., Grant, R. M., Anderson, J. R., Dagg, J. H., Lucie, N. Lancet, 1974, i, 903. Hardy, D. A., Ling, N. R. Nature, 1969, 121, 545.
A. L. FURNISS.
SiR,—The interesting article by Dr Thorsteinsson and a significant error in including the organism formerly referred to as Vibrio fetus among the non-halophilic non-cholera vibrios. Although the latter organism shares the " comma shape of the prototype of the genus Vibrio (V. co/gr), most authorities would now agree that biochemically it is quite dissimilar. Hence, this organism has been regrouped into an entirely separate genus and is properly referred to as Campylobacter fetus.l2 The genus Campylobacter is a member of the family Spirillacea, which includes the genus Spirillum as well as Campylobacter. In contrast, the genus Vibrio is properly a member of the family Vibrionacetv which also includes the genuses Aeromonas Pleisomonas, Photobacterium, and Lucibacterium. All members of the genus Campylobacter are motile, flagellated, microaerophilic, gram-negative organisms. Four subtypes have, to date, been isolated from human sources. others did contain
"
1.
10.
G. I. BARROW.
2.
Buchanan, R. E., Gibbons, N. E. (editors) Bergey’s Manual of Determinative Bacteriology. Baltimore, 1974. Lennette, E. H., Spaulding, E. H., Truant, J. P. (editors). Manual of Clinical Microbiology. American Society for Microbiology, Washington, D.C., 1974.
173
Campylobacter fetus var. fetus has been associated with gastroenteritis, endocarditis, and bacteraemia in man; Campylobacter fetus var. intestinalis, Campylobacter fetus var. jejuni, and Campylobacter sputorum var. sputorum clinical isolates. Of these four the first is clearly established as a human species, only pathogen; the others appear to be predominantly animal pathogens or saprophytic members of the normal human flora which may be pathogenic for man under unusual circumstances. Other members of the genus Campylobacter have also been described whose precise taxonomic position and role in human disease remain unclear. Although confusion has been inevitable in the past because of the poorly defined status and questionable pathogenicity of many of these organisms, it is nonetheless obligatory at this point for both clinicians and microbiologists to adhere to what is now standard taxonomy and nomenclature in referring to these organisms in the literature.
are
the other
adenovirus and herpesvirus infections. Also one single application was effective in the prevention of infection after removal of foreign bodies and after ophthalmic surgery. Moscow Helmholtz
Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, U.S.A.
MICHAEL L. TAPPER.
SOLUBLE OPHTHALMIC DRUG INSERTS SIR,-An experimental and clinical study has been completed on a better way of introducing medication into the eye. Experiments demonstrated the potential of new films (inserts) polyvinylalcohol medicinal ophthalmic mpregnated with antibiotics.1 Yet it was observed 2,
Ophthalmological
Institute, Moscow, U.S.S.R.
common
Y. F. MAICHUK.*
INTRAVENOUS PROSTAGLANDINS AND OXYTOCIN FOR MID-TRIMESTER ABORTION
SIR,-Opinions still vary as to the most effective way of terminating mid-trimester pregnancies, although most clinicians now favour prostaglandins. We report the successful termination of 19 consecutive late first and second trimester pregnancies using a combination of intravenous prostaglandins E2 (P.G.E.2 Upjohn) and
oxytocin (’ Syntocinon’). P.G.E.:(5 mg. in 500 ml. of 5% glucose) was infused into a superficial arm vein at an initial rate of 2-5 (.Lg. per minute, the rate being increased to 5 ;jLg. per minute after half an hour. If after four hours the uterine response was regarded as inadequate
the P.G.E.. infusion was increased to a maximum of 10 jj.g. per minute. To allow ample time for the enhancement phenomenon,’,2 INDUCTION OF ABORTION BY A COMBINATION OF INTRAVENOUS P.G.E.. AND OXYTOCIN
that they, like polypeptide-polysaccharide ocular inserts,33 did not dissolve in the conjunctival sac, and discomfort necessitated their removal from the sac. Therefore soluble ophthalmic drug inserts (S.O.D.I.) have been suggested2 and produced by the Moscow Helmholtz Ophthalmological Institute in collaboration with the All-Union Research Institute for Medical Equipment, U.S.S.R. S.O.D.I. were endorsed for use in ophthalmic practice in the U.S.S.R., following the June 11,1971, decision of the Pharmacological Committee, Ministry of Health. S.O.D.1. are made from polymers of polyacrylamide, ethylacrylate, and vinylpyrrolidone, prepared as thin elastic oval plates with neomycin, kanamycin, sulphamethoxypyrid-
azine, idoxuridine,Florenal ’, atropine, pilocarpine, dexamethasone, and other drugs used in ophthalmology. S.O.D.I. offer a number of advantages over eye-drops (aqueous solutions, viscous solutions of polymers, suspensions), ointments, and subconjunctival injections. In fact, their use makes it possible to achieve prolonged
bioavailability of active substances in the conjunctival fluid and conjunctival and corneal tissue. Though in many of the applications studied S.O.D.I. dissolved in 60-90 minutes, the incorporated active material was found in the conjunctival fluid for up to 34-72 hours. This long duration secures therapeutic concentrations in the conjunctival sac, enhances the penetration of drugs into the tissues and may therefore replace subconjunctival injections in certain cases. This possibility has, of course, to be weighed against tolerance of the active material. However, experience with more than 500 patients (a single application daily or every other day for a maximum of 10 days) demonstrated good tolerance and therapeutic efficacy in different forms of glaucoma, keratitis, iridocyclitis, cornea ulceration, trachoma, conjunctivitis, and 1. 2.
Maichuk, Maichuk,
Y. F. Antibiotiki, 1967, 5, 435. Y. F. in Proceedings of Moscow
Ophthalmological
Conference, 1967, p. 403. 3. Dohlman, C. H., Pavan-Langston, Dr., Rose, J. Ann. Ophthalmol. 1972, 4, 823. 4. Maichuk, Y. F., Khromov, G. L., Koneva, E. B., Tishina, I. F., Pozdnijkov, V. I. in Proceedings of Conference on Ophthalmology, Chuvash, A.S.S.R., 1970, p. 136.
+ = 1 or 2 episodes of vomiting. + + 3 or 4 episodes of vomiting. + + + =more than 4 episodes of vomiting. =
c=complete.
oxytocin
i/c=incomplete.
started two hours after the P.G.E’2 and infused at a of 128 mu per minute. Mixing the P.G.E., and in the same bottle of 5 % glucose had no adverse effects. was
constant rate
oxytocin
Individual results are shown in the accompanying table. The mean total dose of P.G.E’2 used was 5-9 mg.- at an overall rate of 6-1 g. per minute. The average induction/ delivery interval was 16 hours, with only 1 patient (13) taking more than 24 hours. In 13 cases (68%) abortion was
complete. 13 women experienced vomiting, but the nursing staff said that this was distressing in only 2 cases, the remainder responding well to ’Stemetil’ by intramuscular injection. Pain was not a problem and was well controlled by pethidine, the average dose of which was 100 mg.
When the two uterine stimulatants
were run
through the same infusion set, there was a tendency to superficial thrombophlebitis, but this was never anything *
Present address: Regional Adviser, W.H.O., E.M.R.O., P.O., Box 1517, Alexandria, Arab Republic of Egypt.
1. 2.
Brummer, H. C. J. Obstet. Gynœc. Br. Commonw. 1971, 78, 305. Gillespie, A. Br. med. J. 1972, i : 150.
