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FATTY LIVER IN INFANCY
1151 W.H.O. has helped to organise a number of imaginative projects against the treponemal diseases, including those against yaws in Haiti, Thailand, and Indonesia ; against endemic syphilis in the Balkans ; and against bejel in Iraq. By the end of last year no less than four million people had been examined and over one million treated with penicillin in these large operations. The conference drew on the experiences of workers engaged in these projects, and it concentrated particularly on trying to define the unknowns in the disease. Although
has very powerful melanophore-dilating properties in frogs; this activity could not be dissociated from adrenocorticotropic activity in the various preparations which were tried, including Li’s A.C.T.H. peptide. Moreover, in
lating
an increased amount of circuwould be expected, such as Addison’s in conditions of stress-e.g., after an
conditions where
A.C.T.H.
disease, and
operation or a myocardial infarction-patients’ serum an increased power to expand melanophores. Evidence pointing in the same direction is given by older observations that intermedin could cause hypertrophy 8 showed
of the adrenal cortex.7 A.C.T.H. is, of course,
hormone derived from the anterior pituitary gland ; intermedin is said to come from the pars intermedia. This anomaly is unexplained if the two hormones are in fact the same. Dr. F. G. Sulman, in a letter published in this issue, describes a method for the assay of A.C.T.H. in blood, based on the assumption that they are identical. His method involves the separation of an A.C.T.H.-containing fraction of blood, and the assay of its melanophore-expanding activity, in lightada,pted frogs. Should further work prove that this test does in fact measure A.c.T.H., its value will be great ; for unlike other methods it seems not only reliable but simple and cheap. In another paper Sulman 5 calculated that as little as 0-001 µg. of A.C.T.H. will cause darkening of the skin in light-adapted frogs. Moreover, the response can be assessed by measuring microscopically the expansion of individual melanophores in the web of the frog’s foot. When the effect has worn off the frog can be used again ; hypophysectomy of the animals (a procedure which is not well tolerated, except by xenopus toads) does not seem essential, but can be done to prevent interference by endogenous hormones. Such a method of assay, applicable as it is to small amounts of serum, will have obvious uses in studying, more quantitatively than has hitherto been possible, the part played by the human pituitary in many situationse.g., the response of the body to trauma or disease, and the mechanism of salicylate therapy in rheumatic fever. Sulman has also indicated another aspect of the A.C.T.H.-intermedin picture-namely, that A.C.T.H. may We must distinguish cause skin pigmentation in man. here between the darkening of frogs, which is the result of the expansion of individual melanin-bearing cells, and the darkening of man, which is presumably caused by an increase either in the amount of melanin in the specialised cells that make it, or in the number of the cells themselves. Whatever the mechanism, it has been repeatedly noticed that patients receiving A.c.T.H. for more than a few weeks become pigmented, whilst patients on cortisone do not. In addition a pigmented or swarthy skin is a feature of certain conditions where increased adrenocorticotropic activity of the blood is known or suspectedi.e., Addison’s disease, pituitary basophilism, and pregnancy. Thus pigmentation of the skin in Addison’s disease becomes analogous to myxoedema of the connective tissue in primary hypothyroidism 9-a direct effect of an excess of a pituitary hormone deprived of its target organ. CAMPAIGNS AGAINST YAWS THE first International Symposium on Yaws Control was held in March at Bangkok, under the auspices of the World Health Organisation. The meetings took place in the Grand Palace ; and there was later a field trip, excellently organised by the Thai government, in the region of Ubol in north-east Thailand, where the campaign of mass treatment with penicillin was inspected. The conference was attended by delegates of twentythree nations ; those from the United Kingdom included Dr. C. J. Hackett and Dr. R. R. Willcox.
7. Holmquist,
8. 9.
A. G.
a
Klin. Wschr. 1934, 13, 664.
Jores, A., Beck, H. Z. ges. exp. Med. 1934, 94, 293. Watson, E. M., Pearce, R. H. Amer. J. clin. Path. 1949, 19,
442.
direct contact is the most usual mode of infection, the
role, if any, of insect vectors must still be elucidated,
as
must the viability of the spirochaete in moist soil. Treatment in the early stages is simple. A single injection of 1.2 mega-units of a repository penicillin will give reasonable hopes of cure and render the patient noninfectious. Possibly an even smaller dose may suffice, but so far the information does not justify its general use. Other antibiotics, such as aureomycin, terramycin, and chloramphenicol, are effective. The main difficulty, however, is not in treating the established case but in securing the cases to treat. Yaws is usually found at the end of the lines of effective communication in underdeveloped areas lacking permanent medical resources. In such circumstances mass methods of treatment are best ; but experience is already showing that a single mass treatment is insufficient, since some cases are inevitably missed at the first visit, and infectious latent cases, those in the incubation period, and their contacts-as well as the relatively few treatment failures - will cause a recrudescence of the disease in the community. The minimum number of return visits, and the intervals between them, has yet to be determined. It is becoming increasingly apparent that contacts must be examined and treated. Some think of contacts as simply familial residents of the hut ; but yaws is a disease of children, and children play with other children. Realistically, the term " contacts " implies the total child populace of the village, and probably the adult populace as well, and it may be necessary to treat all. Many hope that these imaginative campaigns of yaws control presage the medical, social, and economic improvement of the undeveloped areas. Such a phase of consolidation depends ultimately on the effort of local health administrations. FATTY LIVER IN INFANCY
A FURTHER contribution to the understanding of the nutritional origin of fatty and fibrotic changes in the liver has come appropriately from West Africa, where the name kwashiorkor originated. Silvera and Jelliffe1 have been making liver biopsies in unselected small infants. Using a Silverman needle they chose the anterior subcostal approach whenever the liver was palpable, and if the liver edge could not be felt the puncture was made through the eighth right intercostal space in the mid-axillary line. In some cases examined post mortem liver " biopsy " was performed immediately after death because of difficulties in securing permission for necropsy. The series consists of 13 infants under one year of age and 15 older children between one and eleven years of age. The main interest of the report lies in the younger group, for alterations in the liver amounting in some instances to " extreme generalized fatty change " were in some of the specimens examined even in the All the children in the series first weeks of life. were from poor families. They were all breast-fed for varying periods, andsuckling continued, as is customary among the Yoruba people, up to the age of one or even three vears. These infants are weaned on to food which The result, now is almost exclusively carbohydrate. well recognised, is that soon after weaning is begun,
present
1.
Silvera, W. D., Jelliffe, D. B. J. trop. Med. Hyg. 1952, 55, 73.
1152 "
" - evidence of malignant malnutrition begins to show itself in some of the children. Silvera and Jelliffe, however, report instances of liver changes similar tc those associated with malignant malnutrition in infants still at the breast who seemed otherwise normal from the nutritional aspect. A baby of ten days with ophthalmia neonatorum, and another of twelve days with thrush, showed extreme fatty changes in the liver. It is tempting in such instances to postulate a deficiency in the antenatal supplies to the feetus. Similar changes found in infants later in the first year raise a different, but related, question with regard to the quality of breast-milk. In dealing with breast-feeding among Europeans, it is usually asserted that, whereas quantity may vary, the quality remains essentially the same as regards the main constituents. This has been said to be true even in famine conditions. Silvera and Jelliffe point out, however, that when the diet of the nursing mother is grossly deficient in protein, and when the infant remains at the breast for several years, the composition of the milk may be deficient ; and they suggest that research into this problem would be helpful. Examination of the older children in the series showed liver changes of the type previously reported ; and these changes were essentially the same as in some of the youngest infants. Several babies in the series died of gastro-enteritis, and it is an important negative observation that in such cases the liver was either found to be normal or showed much less change than in the other infants in the series. Even though maternal malnutrition may be a factor in the production of liver changes in these babies, Silvera and Jelliffe urge that early weaning should not be lightly advised, because the alternative is a worse diet of
carbohydrate. FUNGUS INFECTIONS OF THE FEET THE incidence of tinea pedis is much higher in the Services, in sporting fraternities, and among miners than in the general population. This is partly because of the communal use of bathrooms and the sharing of footwear, and partly because the wearing of impermeable footwear for "foot-slogging" or vigorous or heavy exercise or as protection against wet and injury causes retention of sweat and maceration of the skin. The incidence of tinea pedis among the general population is unknown because the mildly afflicted do not In the Forces and among ask for medical attention.
students, however, surveys of fungus infections
can be made with some precision. In the U.S.A. between 37% and 89% have been reported as affected. In this country, Davieshas examined 1050 soldiers and found 645 (61%) with clinical fungus infection. Among new recruits 33% were affected, but in men with 6-18 months’ service- the proportion rose to 76%, while in those with 11/2-6 years’ service it was’75%. Davies’s figures include cases where the infection was minimal or slight, consisting of scaling_ and cracking between one or two toes. These cases are questionable ; but, subtracting them, there remains a clear incidence of 23% in all groups and 11% in recruits. Walker2 found a lower incidence among 1010 recruits examined ; questionable signs were present in 12% and definite signs in 3%. Two facts are of great importance. Firstly, a carrier may have no clinical signs of infection 3 ; Walker found 9 carriers, all of Trichophyton interdigitale, amung 39 recruits from whom positive cultures were obtained. Secondly, the presence of sodden, peeling, fissured skin in the clefts between the fourth and fifth toes does not necessarily imply fungus infection. Simple intertrigo from retention of sweat and chafing, brought on by ·
1. Davies, A. J. J. R. Army med. Cps, 1952, 98, 99. 2. Walker, J. Brit. J. Derm. Syph. 1950, 62, 239. Bull. Johns 3. Ajello, L., Keeney, E. L., Broyles, E. N. Hosp. 1945, 77, 440.
Hopk.
crowding of the toes as a result of shrunken, impermeable socks and heavy footwear, can give a similar appearance; and secondary infection with banal skin organisms may then cause an intertriginous dermatitis. The organism most often responsible for tinea pedis is T. interdigitale, and the next most common organisms are Epidermophyton flocco8um and ’1’. rubrum. T. rubrum is notoriously resistant to all forms of treatment. Originating in South-East Asia, it was brought into this country by many who served during the late war in ’ South-East Asia. In adults it causes chronic desquama. ting lesions and often affects the nails; and reinfection of the skin from the diseased nails is one reason for the persistence of this type of infection. Rarely the infecting organism is not a fungus but monilia. It is likely that monilia can establish itself only when the balance of the skin bacterial flora has been disturbed in some way -for example, by excessive humidity or alkalinity, or from the use of certain antibiotics, or with diabetes mellitus. Davies compared the therapeutic efficacy of Whit. field’s ointment, Castellani’s paint, 1% dithranol oint. ment, and brilliant-green. He found dithranol the most effective remedy, but at the same time the most likely to cause severe reactions. Castellani’s paint was almost as effective, with occasional recurrences and milder reactions. Whitfield’s ointment and brilliantgreen were both relatively ineffective, and their use The newer fungicides was often followed by relapses. have not fulfilled early hopes. The use of phenyl mercuric nitrate for instance, is liable to lead to sensitisation ; while zinc undecylenate is relatively ineffective. The best results follow application of Castellani’s paint at night and a 3% salicylic acid powder in the morning, preceded if necessary by permanganate soaks and accompanied by the daily changing and sterilisation of socks. The treatment of boots and shoes with formalin is of doubtful value. The risk of recurrence is increased by hyperidrosis. The usual mode of transmission is uncertain ; but Riddell4 states that the majority of cases probably represent a recrudescence of infection following a period of local immunity, rather than a new infection by organisms living saprophyticary on floors or baths. Our special need is for a fungicide effective T. rubrum. against SERUM TESTS FOR SYPHILIS of early syphilis is usually clear-cut, taking into account the history, clinical signs, darkground examination for spirochaetes in the lesions, and serum tests. Many of these patients seek treatment and the sera of two-fifths of them remain promptly ; negative, while of those that become seropositive most return to negative fairly soon. With the residue, however -the Wassermann-fast reactors-the question whether treatment has been adequate has to be answered. In the last few years this question has been complicated by the employment of cardiolipin as the antigen in the Wassermann reaction ; for this increases the sensitivity of the test so that in such cases the reaction remains THE
diagnosis
positive longer.55 the last decade a further problem has arisen, the practice of subjecting relatively large sections of the population, such as blood-donors and pregnant women, to routine serum tests. Inevitably
During owing to
some of these people have a positive Wassermann reaction. Of 6809 antenatal patients tested in London the years 1949-51 44 (0-64%) had positive serum during tests.6s Some of these " concealed Wassermann-positive reactors " have a history of treated syphilis ; but in the absence of any clinical history or evidence of syphilis other than the positive blood test, diagnosis is difficult. Some
4. Riddell, R. W. Brit. med. Bull. 1951, 7, 197. 5. Price, I. N. O., Wilkinson, A. E. Brit. J. vener. Dis, 1952, 28, 16. 6. Price, I. N. O. Personal communication.
has very powerful melanophore-dilating properties in frogs; this activity could not be dissociated from adrenocorticotropic activity in the various preparations which were tried, including Li’s A.C.T.H. peptide. Moreover, in
lating
an increased amount of circuwould be expected, such as Addison’s in conditions of stress-e.g., after an
conditions where
A.C.T.H.
disease, and
operation or a myocardial infarction-patients’ serum an increased power to expand melanophores. Evidence pointing in the same direction is given by older observations that intermedin could cause hypertrophy 8 showed
of the adrenal cortex.7 A.C.T.H. is, of course,
hormone derived from the anterior pituitary gland ; intermedin is said to come from the pars intermedia. This anomaly is unexplained if the two hormones are in fact the same. Dr. F. G. Sulman, in a letter published in this issue, describes a method for the assay of A.C.T.H. in blood, based on the assumption that they are identical. His method involves the separation of an A.C.T.H.-containing fraction of blood, and the assay of its melanophore-expanding activity, in lightada,pted frogs. Should further work prove that this test does in fact measure A.c.T.H., its value will be great ; for unlike other methods it seems not only reliable but simple and cheap. In another paper Sulman 5 calculated that as little as 0-001 µg. of A.C.T.H. will cause darkening of the skin in light-adapted frogs. Moreover, the response can be assessed by measuring microscopically the expansion of individual melanophores in the web of the frog’s foot. When the effect has worn off the frog can be used again ; hypophysectomy of the animals (a procedure which is not well tolerated, except by xenopus toads) does not seem essential, but can be done to prevent interference by endogenous hormones. Such a method of assay, applicable as it is to small amounts of serum, will have obvious uses in studying, more quantitatively than has hitherto been possible, the part played by the human pituitary in many situationse.g., the response of the body to trauma or disease, and the mechanism of salicylate therapy in rheumatic fever. Sulman has also indicated another aspect of the A.C.T.H.-intermedin picture-namely, that A.C.T.H. may We must distinguish cause skin pigmentation in man. here between the darkening of frogs, which is the result of the expansion of individual melanin-bearing cells, and the darkening of man, which is presumably caused by an increase either in the amount of melanin in the specialised cells that make it, or in the number of the cells themselves. Whatever the mechanism, it has been repeatedly noticed that patients receiving A.c.T.H. for more than a few weeks become pigmented, whilst patients on cortisone do not. In addition a pigmented or swarthy skin is a feature of certain conditions where increased adrenocorticotropic activity of the blood is known or suspectedi.e., Addison’s disease, pituitary basophilism, and pregnancy. Thus pigmentation of the skin in Addison’s disease becomes analogous to myxoedema of the connective tissue in primary hypothyroidism 9-a direct effect of an excess of a pituitary hormone deprived of its target organ. CAMPAIGNS AGAINST YAWS THE first International Symposium on Yaws Control was held in March at Bangkok, under the auspices of the World Health Organisation. The meetings took place in the Grand Palace ; and there was later a field trip, excellently organised by the Thai government, in the region of Ubol in north-east Thailand, where the campaign of mass treatment with penicillin was inspected. The conference was attended by delegates of twentythree nations ; those from the United Kingdom included Dr. C. J. Hackett and Dr. R. R. Willcox.
7. Holmquist,
8. 9.
A. G.
a
Klin. Wschr. 1934, 13, 664.
Jores, A., Beck, H. Z. ges. exp. Med. 1934, 94, 293. Watson, E. M., Pearce, R. H. Amer. J. clin. Path. 1949, 19,
442.
direct contact is the most usual mode of infection, the
role, if any, of insect vectors must still be elucidated,
as
must the viability of the spirochaete in moist soil. Treatment in the early stages is simple. A single injection of 1.2 mega-units of a repository penicillin will give reasonable hopes of cure and render the patient noninfectious. Possibly an even smaller dose may suffice, but so far the information does not justify its general use. Other antibiotics, such as aureomycin, terramycin, and chloramphenicol, are effective. The main difficulty, however, is not in treating the established case but in securing the cases to treat. Yaws is usually found at the end of the lines of effective communication in underdeveloped areas lacking permanent medical resources. In such circumstances mass methods of treatment are best ; but experience is already showing that a single mass treatment is insufficient, since some cases are inevitably missed at the first visit, and infectious latent cases, those in the incubation period, and their contacts-as well as the relatively few treatment failures - will cause a recrudescence of the disease in the community. The minimum number of return visits, and the intervals between them, has yet to be determined. It is becoming increasingly apparent that contacts must be examined and treated. Some think of contacts as simply familial residents of the hut ; but yaws is a disease of children, and children play with other children. Realistically, the term " contacts " implies the total child populace of the village, and probably the adult populace as well, and it may be necessary to treat all. Many hope that these imaginative campaigns of yaws control presage the medical, social, and economic improvement of the undeveloped areas. Such a phase of consolidation depends ultimately on the effort of local health administrations. FATTY LIVER IN INFANCY
A FURTHER contribution to the understanding of the nutritional origin of fatty and fibrotic changes in the liver has come appropriately from West Africa, where the name kwashiorkor originated. Silvera and Jelliffe1 have been making liver biopsies in unselected small infants. Using a Silverman needle they chose the anterior subcostal approach whenever the liver was palpable, and if the liver edge could not be felt the puncture was made through the eighth right intercostal space in the mid-axillary line. In some cases examined post mortem liver " biopsy " was performed immediately after death because of difficulties in securing permission for necropsy. The series consists of 13 infants under one year of age and 15 older children between one and eleven years of age. The main interest of the report lies in the younger group, for alterations in the liver amounting in some instances to " extreme generalized fatty change " were in some of the specimens examined even in the All the children in the series first weeks of life. were from poor families. They were all breast-fed for varying periods, andsuckling continued, as is customary among the Yoruba people, up to the age of one or even three vears. These infants are weaned on to food which The result, now is almost exclusively carbohydrate. well recognised, is that soon after weaning is begun,
present
1.
Silvera, W. D., Jelliffe, D. B. J. trop. Med. Hyg. 1952, 55, 73.
1152 "
" - evidence of malignant malnutrition begins to show itself in some of the children. Silvera and Jelliffe, however, report instances of liver changes similar tc those associated with malignant malnutrition in infants still at the breast who seemed otherwise normal from the nutritional aspect. A baby of ten days with ophthalmia neonatorum, and another of twelve days with thrush, showed extreme fatty changes in the liver. It is tempting in such instances to postulate a deficiency in the antenatal supplies to the feetus. Similar changes found in infants later in the first year raise a different, but related, question with regard to the quality of breast-milk. In dealing with breast-feeding among Europeans, it is usually asserted that, whereas quantity may vary, the quality remains essentially the same as regards the main constituents. This has been said to be true even in famine conditions. Silvera and Jelliffe point out, however, that when the diet of the nursing mother is grossly deficient in protein, and when the infant remains at the breast for several years, the composition of the milk may be deficient ; and they suggest that research into this problem would be helpful. Examination of the older children in the series showed liver changes of the type previously reported ; and these changes were essentially the same as in some of the youngest infants. Several babies in the series died of gastro-enteritis, and it is an important negative observation that in such cases the liver was either found to be normal or showed much less change than in the other infants in the series. Even though maternal malnutrition may be a factor in the production of liver changes in these babies, Silvera and Jelliffe urge that early weaning should not be lightly advised, because the alternative is a worse diet of
carbohydrate. FUNGUS INFECTIONS OF THE FEET THE incidence of tinea pedis is much higher in the Services, in sporting fraternities, and among miners than in the general population. This is partly because of the communal use of bathrooms and the sharing of footwear, and partly because the wearing of impermeable footwear for "foot-slogging" or vigorous or heavy exercise or as protection against wet and injury causes retention of sweat and maceration of the skin. The incidence of tinea pedis among the general population is unknown because the mildly afflicted do not In the Forces and among ask for medical attention.
students, however, surveys of fungus infections
can be made with some precision. In the U.S.A. between 37% and 89% have been reported as affected. In this country, Davieshas examined 1050 soldiers and found 645 (61%) with clinical fungus infection. Among new recruits 33% were affected, but in men with 6-18 months’ service- the proportion rose to 76%, while in those with 11/2-6 years’ service it was’75%. Davies’s figures include cases where the infection was minimal or slight, consisting of scaling_ and cracking between one or two toes. These cases are questionable ; but, subtracting them, there remains a clear incidence of 23% in all groups and 11% in recruits. Walker2 found a lower incidence among 1010 recruits examined ; questionable signs were present in 12% and definite signs in 3%. Two facts are of great importance. Firstly, a carrier may have no clinical signs of infection 3 ; Walker found 9 carriers, all of Trichophyton interdigitale, amung 39 recruits from whom positive cultures were obtained. Secondly, the presence of sodden, peeling, fissured skin in the clefts between the fourth and fifth toes does not necessarily imply fungus infection. Simple intertrigo from retention of sweat and chafing, brought on by ·
1. Davies, A. J. J. R. Army med. Cps, 1952, 98, 99. 2. Walker, J. Brit. J. Derm. Syph. 1950, 62, 239. Bull. Johns 3. Ajello, L., Keeney, E. L., Broyles, E. N. Hosp. 1945, 77, 440.
Hopk.
crowding of the toes as a result of shrunken, impermeable socks and heavy footwear, can give a similar appearance; and secondary infection with banal skin organisms may then cause an intertriginous dermatitis. The organism most often responsible for tinea pedis is T. interdigitale, and the next most common organisms are Epidermophyton flocco8um and ’1’. rubrum. T. rubrum is notoriously resistant to all forms of treatment. Originating in South-East Asia, it was brought into this country by many who served during the late war in ’ South-East Asia. In adults it causes chronic desquama. ting lesions and often affects the nails; and reinfection of the skin from the diseased nails is one reason for the persistence of this type of infection. Rarely the infecting organism is not a fungus but monilia. It is likely that monilia can establish itself only when the balance of the skin bacterial flora has been disturbed in some way -for example, by excessive humidity or alkalinity, or from the use of certain antibiotics, or with diabetes mellitus. Davies compared the therapeutic efficacy of Whit. field’s ointment, Castellani’s paint, 1% dithranol oint. ment, and brilliant-green. He found dithranol the most effective remedy, but at the same time the most likely to cause severe reactions. Castellani’s paint was almost as effective, with occasional recurrences and milder reactions. Whitfield’s ointment and brilliantgreen were both relatively ineffective, and their use The newer fungicides was often followed by relapses. have not fulfilled early hopes. The use of phenyl mercuric nitrate for instance, is liable to lead to sensitisation ; while zinc undecylenate is relatively ineffective. The best results follow application of Castellani’s paint at night and a 3% salicylic acid powder in the morning, preceded if necessary by permanganate soaks and accompanied by the daily changing and sterilisation of socks. The treatment of boots and shoes with formalin is of doubtful value. The risk of recurrence is increased by hyperidrosis. The usual mode of transmission is uncertain ; but Riddell4 states that the majority of cases probably represent a recrudescence of infection following a period of local immunity, rather than a new infection by organisms living saprophyticary on floors or baths. Our special need is for a fungicide effective T. rubrum. against SERUM TESTS FOR SYPHILIS of early syphilis is usually clear-cut, taking into account the history, clinical signs, darkground examination for spirochaetes in the lesions, and serum tests. Many of these patients seek treatment and the sera of two-fifths of them remain promptly ; negative, while of those that become seropositive most return to negative fairly soon. With the residue, however -the Wassermann-fast reactors-the question whether treatment has been adequate has to be answered. In the last few years this question has been complicated by the employment of cardiolipin as the antigen in the Wassermann reaction ; for this increases the sensitivity of the test so that in such cases the reaction remains THE
diagnosis
positive longer.55 the last decade a further problem has arisen, the practice of subjecting relatively large sections of the population, such as blood-donors and pregnant women, to routine serum tests. Inevitably
During owing to
some of these people have a positive Wassermann reaction. Of 6809 antenatal patients tested in London the years 1949-51 44 (0-64%) had positive serum during tests.6s Some of these " concealed Wassermann-positive reactors " have a history of treated syphilis ; but in the absence of any clinical history or evidence of syphilis other than the positive blood test, diagnosis is difficult. Some
4. Riddell, R. W. Brit. med. Bull. 1951, 7, 197. 5. Price, I. N. O., Wilkinson, A. E. Brit. J. vener. Dis, 1952, 28, 16. 6. Price, I. N. O. Personal communication.