- Email: [email protected]
CHROMOSOME ANALYSIS FROM CAPILLARY BLOOD
328 this method that the resulting appointments system is designed fit the way the clinic is actually run, without affecting its internal organisation at all. Also the graphs provide all the evidence needed for designing and maintaining low levels of waiting, and the method is not invalidated by regular differences in length of consultation, nor by planned breaks. In fact, the graphical evidence may bring these differences and planned breaks to the attention of the designer of the appointments systems, who may then make the necessary allowance. I must agree with Dr. Pike and Miss Blanco White, though, that the primary need is for an appreciation of the to
necessity for efficient appointments systems. These can only be in favour of doctors, patients, and administrators alike. M.R.C. Pneumoconiosis Research
Llandough Hospital, Penarth, Glamorgan.
Unit,
C. E. ROSSITER.
POSTMORTEM NUCLEAR SEXING
SIR,-Population studies on chromosomal anomalies which are reflected by anomalous nuclear sex are most conveniently conducted at birth or at death. So far only the former have been carried out on an extensive scale: such studies are a satisfactory source of populaincidence at a defined age, they have the disadvantages tion that mortality studies require follow-up and that inclusive data on mortality cannot be available this century. A more direct approach in relating nuclear sex to mortality is to study populations at necropsy in communities in which the necropsy rate is high. This is very simple since the conventional buccal smear techniques, when applied to the mucosa of the urinary bladder, give preparations which are greatly superior to any which can be obtained with equal simplicity in the living. As the great majority of these nuclei show Barr bodies in the normal female a cursory glance would reveal any substantial mosaicism in X chromosome number, a condition which, in the commoner known varieties, would be extremely difficult to detect on buccal smears, particularly in the newborn. Further, if any anomaly is found, tissues are readily available, and the karyotype may be determined and extensive histological or other studies made of the gonads. For the past eighteen months a screening procedure has been in routine use in all necropsies taking place in this hospital in infants under six months. Bladder smears are made on a slide marked only by the surname: the nuclear sex is determined, and further studies pursued if there is any inconsistency, or any peculiarity of the sex chromatin. The routine determination of nuclear sex at necropsy would not only provide extensive data on both the incidence and the mortality experience of persons with abnormal nuclear sex; it would also increase the proportion of laboratories whose repertoire includes the ability to carry out this simple test with precision. At present only a few specialised centres carry out nuclear sexing sufficiently frequently to maintain the techniques involved at an adequate standard for reliable diagnosis. Apart from absence of Barr bodies in some girls on whom necropsy was delayed for more than two days no difficulties in interpretation have been experienced. This tendency for Barr bodies to fade after death may explain part of the male preponderance reputed to occur in spontaneous abortions. It may also be worth pointing out that extensive series of mucosal smears, which reveal excellent morphology of the Barr body, are available as a byproduct of cervical smears. The majority of such smears also provide areas which are effectively white-cell concentrates; in many slides nuclear sexing may be carried out on at least two
although
types of epithelium and
on
polymorphs. Unfortunatelc,
although the indications for cervical smear are increasing rapidly, and in some centres include both sterility and pregnancy, few observers of these smears comment on their nuclear
sex.
Department of Social Medicine and Institute of Child Health, University of Birmingham.
J. H. EDWARDS.
Department of Pathology, The Children’s
Hospital, Birmingham.
A. H. CAMERON.
PARTIAL MONOSOMY 18 AND ANOMALY OF THYROXINE SYNTHESIS
SIR,-In relation to the letter by Biihler et al. (Jan.18), it may be noted that the association between chromosomal mosaicism and Pendred’s syndrome1 has been described by Heni and Siebner.2 Chromosome analysis revealed triple stem-line mosaicism. Cells with 46 chromosomes had a normal karyotype. Cells with 47 chromosomes (20-24%) had an extra chromosome similar to no. 16, In the cells with 45 (9-52%) there were two missing chromosomes from group C (6-12, X), and an additional chromosome in group A (1-3), probably produced by reciprocal translocation. Department of Anatomy, Queen’s University, Belfast.
M. NABIL RASHAD.
your issue of
Jan. 18, Dr. Buhler and his of the short arms of a chromo. deletion colleagues report some 18. Although I described, exactly one year ago,’i the first example of this chromosome aberration, they do not quote my work. I have heard that other cases are now known and should be published. It thus seems that the chromosome-18 deletion may be a well-defined syndrome, and for that reason I wish to draw attention to my first paper. SIR,-In
a
Clinique de Génétique Médicale, Hôpital des Enfants-Malades, Paris XVe.
JEAN
DE
GROUCHY,
CHROMOSOME ANALYSIS FROM CAPILLARY BLOOD
SiR,ņSince the description of the Moorhead method’5 for preparation of chromosomes from peripheral blood, many simplifications and modifications have been described. For chromosome analysis in the newborn, there has been great need of a method in which capillary blood can be used. A few have already been described In this laboratory a micromethod, based on that of Moorhead, has yielded good results with as little as two drops of blood. 1. The culture medium is
prepared as described by Harndenfrom serum, and 70% T.C.199
10% chick embryo extract, 20% human AB
(Glaxo). 2. 0-2 ml. heparin (’ Liquenin ’, Roche) is added to 6 ml. of this medium in a I-oz. universal container. 3. Phytohxmagglutinin is added (0-2 ml. ’ Difco P’, or 0.25 ml. of the Burroughs Wellcome preparation). 4. Two drops of blood are allowed to drip from a finger prick ora heel stab into the bottle, which is shaken gently to prevent clottina, 5. The bottle is gassed with 5% CO, in air, and then incub3tlJ at 37=C. 6. After incubation for three days (’ Colcemid’, Ciba) is addej 1. Pendred, V. Lancet, 1896, ii, 532. 2. Heni, F., Siebner, H. Klin. Wschr. 1963, 41. 1038. 3. de Grouchy, J., Lamy, M., Thieffry, S., Arthuis, M., Salmon. Dysmorphie complexe avec oligophrénie: délétion des bras cours d’un chromosome 17-18. C.R. Acad. Sci., Paris, 1963, 256, 1025. 4. Thieffry, S., Arthuis, M., de Grouchy, J. de, Lamy, M., Salmon. Délétion des bras courts d’un chromosome 17-18: dysmerp complexe avec oligophrénie. Arch. franç. Pédiat. 1963, 20, 740 5. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D M Hungerford, D. A. Exp. Cell Res. 1960, 20, 613. 6. Frøland A. Lancet, 1962, ii, 1281. 7. Edwards, J. H. Cytogenetics, 1962, 1, 90. 8. Arakaki, D. T., Sparkes, R. S. 1963, ibid. 2, 57. 9. Harnden, D. G. Brit. J. exp. Path. 1960, 41, 31.
329 0’4 ml. of
0-02%
to
each
further three to four hours.
bottle) and incubation is continued for
a
method, hypotonic pretreatment in 0-8% sodmm citrate (20 min. at 37’C), fixation in 1/3 glacia1-acetic-acid/ ethanol. and the making of air-dried preparations are carried out. This technique has also been used successfully with blood from the tail vein of rats. J. S. ROBINSON N. P. BISHUN of M. N. RASHAD Department Anatomy, Queen’s University, W. R. M. MORTON. 7. Belfast, 7. As in Moorhead’s
TWO RED-CELL POPULATIONS IN THE HUMAN FEMALE HETEROZYGOUS FOR G.-6-P.D. DEFICIENCY
SIR,-In 1962 Beutlerpostulated that, in the human female heterozygous for G.-6-P.D. deficiency, erythrocytes
represented a mosaic consisting of cells with normal enzyme activity and of cells with grossly deficient enzyme activity. He derived his opinion by the hypothesis of Ohno2 and Lyon,3 according to whom only one of the two X-chromosomes is active. He tested this hypothesis indirectly, using the G.S.H. stability test and the methxmoglobin reduction test. He compared the curves of artificial blood mixtures and that of female blood with intermediate level of G.-6-P.D. We have been able to confirm the Lyon-Beutler hypothesis using a direct method. On blood smears of females heterozygous for the G.-6-P.D. deficiency we demonstrated the presence of a double red-cell population. Blood was first treated by Brewer’s method (the so-called methxmoglobin reduction test).4 Then smears were prepared on which the Kleihauer and Betke technique5 was applied. With this (not yet published) technique, methasmoglobin in the single red cell can be demonstrated. We performed our
experiments
on
6
heterozygous females,
on
many
normal individuals, and on subjects with past history of favism. We also prepared artificial mixtures of normal and G.-6-P.D.-deficient blood. G. SANSONE Department of Human Genetics of the University of Genova, and Pediatric A. RASORE-QUARTINO Department of the Galliera Hospital, G. VENEZIANO. Genova, Italy. RECURRING ULCERS OF THE MOUTH SIR,-Your annotation of Dec. 21 demands a small note
of caution. the large majority of such cases, you are quite stating that this " is a minor illness ". In a small proportion,’ however, recurrent aphthous ulcers may be the associated dermatologic manifestation of a more serious multisystem condition, Behçet’s disease. A mortality-rate of 49% was found by myself and others 7 among cases of Behcet’s As
TREATMENT OF BASAL-CELL CARCINOMA
SIR,-Your leader1 on the treatment of basal-cell carcinoma asks for more persuasive evidence of the value of electrodesiccation and curettage. We reported 22 recurrences (7-7%) in 287 lesions of basal-cell carcinoma treated by electrodesiccation and curettage.22 Two types of basal-cell carcinoma not mentioned by you are: (1) the multiple (up to 50) small lesions in patients with the so-called basal-cell nsevoid syndrome (Gorlin-Goltz syndrome)3 or in patients with multiple lesions developing in irradiated areas; and (2) the superficial multicentric type. In both of these types, electrodesiccation and curettage is the treatment of choice. We have found this technique very satisfactory also for the treatment of small peripheral recurrences
following plastic
surgery
or
radiotherapy.
Electrodesiccation and curettage is not a panacea for all basal-cell carcinomas. Accurate diagnosis (by biopsy) with classification of the tumour type is still a prerequisite. The technique must be studied and practised. That failures may occur is freely admitted, but with experience in selecting appropriate cases the rate of cure on balance should be about 95%. Ottawa Civic Hospital Clinic, Ontario Cancer Treatment and Research Foundation, Ottawa, Ontario.
GEO. S. WILLIAMSON ROBERT JACKSON.
MARBORAN IN HERPES GENITALIS
SIR,-N-methylisatin -thiosemicarbazone (Compound 33 T 57; methisazone; ’Marboran’) has been found beneficial in variola 4: and this raised the possibility of using it in other virus diseases. Experimentally, it has been shown to have no effect on the herpes-simplex virus; but experimental evidence does not always indicate the clinical effects of a drug, and we therefore decided to try it in the treatment of genital herpetic lesions. Marboran was given to 6 patients (5 male and 1 female), with herpes genitalis. Their average age was 27 years, ranging from 18 to 41. 4 were from the United Kingdom and 2 were from the West Indies. Syphilis was excluded by three repeated darkground examinations of all the lesions and repeated Wassermann and Kahn tests over three months. In all cases the tests were
negative.
The herpes-simplex virus was isolated from the lesions and cultured on the chorioallantois of chick-embryos in all cases. Marboran was administered orally in a dose of 1-0 g. three times daily for two days only; for if it were to have any effects on the virus these were likely to be manifest during this period. The patients were instructed to return at intervals of two to The results are three days until the lesions had healed. summarised in table I.
regards
correct
in
TABLE I-RESULTS OF TREATMENT WITH MARBORAN IN HERPES GENITALIS
disease in which the central nervous system was involved. A favourable response to the use of large doses of corticosteroids was suggested by the course of one patient in our report. Although a satisfactory outcome may be expected in most patients presenting with recurrent aphthous ulcers, a careful inquiry should always be made concerning the presence of ophthalmoloeical and neurological symptoms. Neurology Service,
William Beaumont General Hospital, El Paso, Texas, U.S.A.
HARRY H. WHITE.
Beutler, E., Yeh, M., Fairbanks, V. F. Proc. nat. Acad. Sci. 1962, 48, 9. Ohno, S., Hauschka, T. S. Cancer Res. 1960, 20, 541. Lyon, M. F. Nature, Lond. 1961, 190, 372. Brewer, G. J., Tarlow, A. R., Alving, A. S. Bull. Wld Hlth Org. 1960, 22, 633. 5 Kleihauer, E., Betke, K. Personal communication. 6 Ship, I. I, Merritt, A. D., Stanley, H. R. Amer. J. Med. 1962, 32, 32. 7 Schotland, D. L., Wolf, S. M., White, H. H., Dubin, H. V. ibid. 1963, 34, 544.
1 2 3 4
duration of the lesions after treatment was the mean period from the onset to the disapand days of the lesions was 12-83 days. These results do pearance not compare favourably with those of a topical application The
mean
8-0
1. 2. 3. 4.
Lancet, 1963, ii, 24.
Williamson, G. S., Jackson, R. Canad. med. Ass. J. 1962, 86, 855. Gorlin, R. J., Goltz, R. New Engl. J. Med. 1960, 262, 908. Bauer, D. J., St. Vincent, L., Kempe, C. H., Downie, A. W. Lancet, 1963, ii, 494.
necessity for efficient appointments systems. These can only be in favour of doctors, patients, and administrators alike. M.R.C. Pneumoconiosis Research
Llandough Hospital, Penarth, Glamorgan.
Unit,
C. E. ROSSITER.
POSTMORTEM NUCLEAR SEXING
SIR,-Population studies on chromosomal anomalies which are reflected by anomalous nuclear sex are most conveniently conducted at birth or at death. So far only the former have been carried out on an extensive scale: such studies are a satisfactory source of populaincidence at a defined age, they have the disadvantages tion that mortality studies require follow-up and that inclusive data on mortality cannot be available this century. A more direct approach in relating nuclear sex to mortality is to study populations at necropsy in communities in which the necropsy rate is high. This is very simple since the conventional buccal smear techniques, when applied to the mucosa of the urinary bladder, give preparations which are greatly superior to any which can be obtained with equal simplicity in the living. As the great majority of these nuclei show Barr bodies in the normal female a cursory glance would reveal any substantial mosaicism in X chromosome number, a condition which, in the commoner known varieties, would be extremely difficult to detect on buccal smears, particularly in the newborn. Further, if any anomaly is found, tissues are readily available, and the karyotype may be determined and extensive histological or other studies made of the gonads. For the past eighteen months a screening procedure has been in routine use in all necropsies taking place in this hospital in infants under six months. Bladder smears are made on a slide marked only by the surname: the nuclear sex is determined, and further studies pursued if there is any inconsistency, or any peculiarity of the sex chromatin. The routine determination of nuclear sex at necropsy would not only provide extensive data on both the incidence and the mortality experience of persons with abnormal nuclear sex; it would also increase the proportion of laboratories whose repertoire includes the ability to carry out this simple test with precision. At present only a few specialised centres carry out nuclear sexing sufficiently frequently to maintain the techniques involved at an adequate standard for reliable diagnosis. Apart from absence of Barr bodies in some girls on whom necropsy was delayed for more than two days no difficulties in interpretation have been experienced. This tendency for Barr bodies to fade after death may explain part of the male preponderance reputed to occur in spontaneous abortions. It may also be worth pointing out that extensive series of mucosal smears, which reveal excellent morphology of the Barr body, are available as a byproduct of cervical smears. The majority of such smears also provide areas which are effectively white-cell concentrates; in many slides nuclear sexing may be carried out on at least two
although
types of epithelium and
on
polymorphs. Unfortunatelc,
although the indications for cervical smear are increasing rapidly, and in some centres include both sterility and pregnancy, few observers of these smears comment on their nuclear
sex.
Department of Social Medicine and Institute of Child Health, University of Birmingham.
J. H. EDWARDS.
Department of Pathology, The Children’s
Hospital, Birmingham.
A. H. CAMERON.
PARTIAL MONOSOMY 18 AND ANOMALY OF THYROXINE SYNTHESIS
SIR,-In relation to the letter by Biihler et al. (Jan.18), it may be noted that the association between chromosomal mosaicism and Pendred’s syndrome1 has been described by Heni and Siebner.2 Chromosome analysis revealed triple stem-line mosaicism. Cells with 46 chromosomes had a normal karyotype. Cells with 47 chromosomes (20-24%) had an extra chromosome similar to no. 16, In the cells with 45 (9-52%) there were two missing chromosomes from group C (6-12, X), and an additional chromosome in group A (1-3), probably produced by reciprocal translocation. Department of Anatomy, Queen’s University, Belfast.
M. NABIL RASHAD.
your issue of
Jan. 18, Dr. Buhler and his of the short arms of a chromo. deletion colleagues report some 18. Although I described, exactly one year ago,’i the first example of this chromosome aberration, they do not quote my work. I have heard that other cases are now known and should be published. It thus seems that the chromosome-18 deletion may be a well-defined syndrome, and for that reason I wish to draw attention to my first paper. SIR,-In
a
Clinique de Génétique Médicale, Hôpital des Enfants-Malades, Paris XVe.
JEAN
DE
GROUCHY,
CHROMOSOME ANALYSIS FROM CAPILLARY BLOOD
SiR,ņSince the description of the Moorhead method’5 for preparation of chromosomes from peripheral blood, many simplifications and modifications have been described. For chromosome analysis in the newborn, there has been great need of a method in which capillary blood can be used. A few have already been described In this laboratory a micromethod, based on that of Moorhead, has yielded good results with as little as two drops of blood. 1. The culture medium is
prepared as described by Harndenfrom serum, and 70% T.C.199
10% chick embryo extract, 20% human AB
(Glaxo). 2. 0-2 ml. heparin (’ Liquenin ’, Roche) is added to 6 ml. of this medium in a I-oz. universal container. 3. Phytohxmagglutinin is added (0-2 ml. ’ Difco P’, or 0.25 ml. of the Burroughs Wellcome preparation). 4. Two drops of blood are allowed to drip from a finger prick ora heel stab into the bottle, which is shaken gently to prevent clottina, 5. The bottle is gassed with 5% CO, in air, and then incub3tlJ at 37=C. 6. After incubation for three days (’ Colcemid’, Ciba) is addej 1. Pendred, V. Lancet, 1896, ii, 532. 2. Heni, F., Siebner, H. Klin. Wschr. 1963, 41. 1038. 3. de Grouchy, J., Lamy, M., Thieffry, S., Arthuis, M., Salmon. Dysmorphie complexe avec oligophrénie: délétion des bras cours d’un chromosome 17-18. C.R. Acad. Sci., Paris, 1963, 256, 1025. 4. Thieffry, S., Arthuis, M., de Grouchy, J. de, Lamy, M., Salmon. Délétion des bras courts d’un chromosome 17-18: dysmerp complexe avec oligophrénie. Arch. franç. Pédiat. 1963, 20, 740 5. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D M Hungerford, D. A. Exp. Cell Res. 1960, 20, 613. 6. Frøland A. Lancet, 1962, ii, 1281. 7. Edwards, J. H. Cytogenetics, 1962, 1, 90. 8. Arakaki, D. T., Sparkes, R. S. 1963, ibid. 2, 57. 9. Harnden, D. G. Brit. J. exp. Path. 1960, 41, 31.
329 0’4 ml. of
0-02%
to
each
further three to four hours.
bottle) and incubation is continued for
a
method, hypotonic pretreatment in 0-8% sodmm citrate (20 min. at 37’C), fixation in 1/3 glacia1-acetic-acid/ ethanol. and the making of air-dried preparations are carried out. This technique has also been used successfully with blood from the tail vein of rats. J. S. ROBINSON N. P. BISHUN of M. N. RASHAD Department Anatomy, Queen’s University, W. R. M. MORTON. 7. Belfast, 7. As in Moorhead’s
TWO RED-CELL POPULATIONS IN THE HUMAN FEMALE HETEROZYGOUS FOR G.-6-P.D. DEFICIENCY
SIR,-In 1962 Beutlerpostulated that, in the human female heterozygous for G.-6-P.D. deficiency, erythrocytes
represented a mosaic consisting of cells with normal enzyme activity and of cells with grossly deficient enzyme activity. He derived his opinion by the hypothesis of Ohno2 and Lyon,3 according to whom only one of the two X-chromosomes is active. He tested this hypothesis indirectly, using the G.S.H. stability test and the methxmoglobin reduction test. He compared the curves of artificial blood mixtures and that of female blood with intermediate level of G.-6-P.D. We have been able to confirm the Lyon-Beutler hypothesis using a direct method. On blood smears of females heterozygous for the G.-6-P.D. deficiency we demonstrated the presence of a double red-cell population. Blood was first treated by Brewer’s method (the so-called methxmoglobin reduction test).4 Then smears were prepared on which the Kleihauer and Betke technique5 was applied. With this (not yet published) technique, methasmoglobin in the single red cell can be demonstrated. We performed our
experiments
on
6
heterozygous females,
on
many
normal individuals, and on subjects with past history of favism. We also prepared artificial mixtures of normal and G.-6-P.D.-deficient blood. G. SANSONE Department of Human Genetics of the University of Genova, and Pediatric A. RASORE-QUARTINO Department of the Galliera Hospital, G. VENEZIANO. Genova, Italy. RECURRING ULCERS OF THE MOUTH SIR,-Your annotation of Dec. 21 demands a small note
of caution. the large majority of such cases, you are quite stating that this " is a minor illness ". In a small proportion,’ however, recurrent aphthous ulcers may be the associated dermatologic manifestation of a more serious multisystem condition, Behçet’s disease. A mortality-rate of 49% was found by myself and others 7 among cases of Behcet’s As
TREATMENT OF BASAL-CELL CARCINOMA
SIR,-Your leader1 on the treatment of basal-cell carcinoma asks for more persuasive evidence of the value of electrodesiccation and curettage. We reported 22 recurrences (7-7%) in 287 lesions of basal-cell carcinoma treated by electrodesiccation and curettage.22 Two types of basal-cell carcinoma not mentioned by you are: (1) the multiple (up to 50) small lesions in patients with the so-called basal-cell nsevoid syndrome (Gorlin-Goltz syndrome)3 or in patients with multiple lesions developing in irradiated areas; and (2) the superficial multicentric type. In both of these types, electrodesiccation and curettage is the treatment of choice. We have found this technique very satisfactory also for the treatment of small peripheral recurrences
following plastic
surgery
or
radiotherapy.
Electrodesiccation and curettage is not a panacea for all basal-cell carcinomas. Accurate diagnosis (by biopsy) with classification of the tumour type is still a prerequisite. The technique must be studied and practised. That failures may occur is freely admitted, but with experience in selecting appropriate cases the rate of cure on balance should be about 95%. Ottawa Civic Hospital Clinic, Ontario Cancer Treatment and Research Foundation, Ottawa, Ontario.
GEO. S. WILLIAMSON ROBERT JACKSON.
MARBORAN IN HERPES GENITALIS
SIR,-N-methylisatin -thiosemicarbazone (Compound 33 T 57; methisazone; ’Marboran’) has been found beneficial in variola 4: and this raised the possibility of using it in other virus diseases. Experimentally, it has been shown to have no effect on the herpes-simplex virus; but experimental evidence does not always indicate the clinical effects of a drug, and we therefore decided to try it in the treatment of genital herpetic lesions. Marboran was given to 6 patients (5 male and 1 female), with herpes genitalis. Their average age was 27 years, ranging from 18 to 41. 4 were from the United Kingdom and 2 were from the West Indies. Syphilis was excluded by three repeated darkground examinations of all the lesions and repeated Wassermann and Kahn tests over three months. In all cases the tests were
negative.
The herpes-simplex virus was isolated from the lesions and cultured on the chorioallantois of chick-embryos in all cases. Marboran was administered orally in a dose of 1-0 g. three times daily for two days only; for if it were to have any effects on the virus these were likely to be manifest during this period. The patients were instructed to return at intervals of two to The results are three days until the lesions had healed. summarised in table I.
regards
correct
in
TABLE I-RESULTS OF TREATMENT WITH MARBORAN IN HERPES GENITALIS
disease in which the central nervous system was involved. A favourable response to the use of large doses of corticosteroids was suggested by the course of one patient in our report. Although a satisfactory outcome may be expected in most patients presenting with recurrent aphthous ulcers, a careful inquiry should always be made concerning the presence of ophthalmoloeical and neurological symptoms. Neurology Service,
William Beaumont General Hospital, El Paso, Texas, U.S.A.
HARRY H. WHITE.
Beutler, E., Yeh, M., Fairbanks, V. F. Proc. nat. Acad. Sci. 1962, 48, 9. Ohno, S., Hauschka, T. S. Cancer Res. 1960, 20, 541. Lyon, M. F. Nature, Lond. 1961, 190, 372. Brewer, G. J., Tarlow, A. R., Alving, A. S. Bull. Wld Hlth Org. 1960, 22, 633. 5 Kleihauer, E., Betke, K. Personal communication. 6 Ship, I. I, Merritt, A. D., Stanley, H. R. Amer. J. Med. 1962, 32, 32. 7 Schotland, D. L., Wolf, S. M., White, H. H., Dubin, H. V. ibid. 1963, 34, 544.
1 2 3 4
duration of the lesions after treatment was the mean period from the onset to the disapand days of the lesions was 12-83 days. These results do pearance not compare favourably with those of a topical application The
mean
8-0
1. 2. 3. 4.
Lancet, 1963, ii, 24.
Williamson, G. S., Jackson, R. Canad. med. Ass. J. 1962, 86, 855. Gorlin, R. J., Goltz, R. New Engl. J. Med. 1960, 262, 908. Bauer, D. J., St. Vincent, L., Kempe, C. H., Downie, A. W. Lancet, 1963, ii, 494.