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AMINO-ACIDS TO INCREASE PERIPHERAL BLOOD
953 took the swabs, the conditions were the same. This time, the immunised yielded 2 carriers and the nonimmunised none. With the exception of one avirulent mitis strain, all the 0. diphthericu recovered were of the intermedius type (the cause of the few cases of clinical diphtheria in the city hospital). Soothill points out that, though still not statistically significant, these figures are comparable with those reported by the L.C.C. Public Health Department.4 A parallel investigation in June, 1944, among 200 adults, mainly factory workers, drawn from widely separated parts of Norwich produced completely negative results. Though gratified as an epidemiologist, Soothill is still unsatisfied as a statistician, and he asks for more investigations of carrier-rates among immunes and nonimmunes, account being taken not only of the state of immunity but also of the degree of exposure. It is useless, as he says, to compare closed with open communities. In the former immunisation may not prevent a temporary rise in the carrier-rate if diphtheria is endemic,6 but in communities where immunisation is extended to the greater part of the most susceptible population-the pre-school and school childrenMcKinnon s points out that there is a fall in the incidence of clinical cases and carriers and that both classes in the end virtually disappear. Thus in Toronto (population
650,000) 1098
swabs
in
cases were
pre-immunisation year, there were of diphtheria with 90 deaths, and 13,231 examined of which 2564 were positive. In 1926,
a
1936, when 104,449 persons immunised, there were 48
known to have been of diphtheria with 2 deaths, and 4307 swabs were examined of which 80 were positive. In 1937, surveys of 1774 school-children The figures for in Montreal yielded only 2 carriers. Canadian cities in 1947, ten years later, when they are published, should be conclusive enough to satisfy the most sceptical. AMINO-ACIDS TO
were
cases
INCREASE
PERIPHERAL BLOOD
PROTEINS by virtue of their specific dynamic action are well known to increase heat-production in the body, but there is some doubt whether this increase is accompanied by a rise in the skin temperature of the extremities.7 The specific dynamic action of proteins mainly depends on the presence of a few amino-acids, particularly glycine, alanine, phenylalanine, and tyrosine. Gubner and his colleagues 8 have given glycine in doses of 20 g. by mouth, dissolved in 200-300 ml. of milk, to 25 subjects, some of whom had peripheral vascular disease. In 18 of these the average maximal rise in oxygen consumption above the basal level was 18-4%, but there was a considerable variation in the individual figures and in 4 subjects there was no significant rise in consumption. Skin temperatures were measured in Inormal people and in 4 patients with peripheral vascular disease, and the glycine was found to raise the temperature of toes. and fingers in 3 out of the 4 patients. The rise was greatest in the toes, and the normals showed a rise of 4°C, compared with 2-3°C in the patients. Incases a posterior tibial nerve block was found to have much the same effect as glycine on skin temperature. Glycine produced a significantly greater rise of skin temperature than the ingestion of alcohol. Oscillometric pulsation in the calf was increased after the ingestion of glycine in 8 out of the 11 normal subjects, but in none of the patients with peripheral vascular disease, even though 2 of the patients had significant rises in skin temperature. Blood4. Lancet, 1947, i, 668. 5. Dudley, S. F., May, P. M., O’Flynn, J. A. Spec. Rep. Ser. med. Res. Coun., Lond. 1934, no. 195. 6. McKinnon, N. E., in Control of Common Fevers, London, 1942,
p. 47.
7. 8.
Richards, R. L. Peripheral Circulation in Health and Disease, Edinburgh, 1946, p. 35. Gubner, R., Di Palma, J. R., Moore, E. Amer. J. med. Sci. 1947, 213, 46.
as measured by venous occlusion plethysmography, was increased by glycine, the average rise being 62% in 4 normal subjects, and 30-5% in 4 patients with peripheral vascular disease. This increase is the result of peripheral vasodilatation and increased cardiac output. Much of the early work on peripheral vascular diseases has had to be discarded because of faulty technique, so there is a natural tendency to be cautious in accepting new observations. This investigation, however, seems
flow to the extremities,
to have been well controlled, and if it is confirmed it will undoubtedly stimulate others to explore its practical
applications. RISKS OF LOCAL SULPHONAMIDES THE Home Office has drawn the attention of trade and other organisations to the Poisons (Amendment) Rules, 1947, which were made by the Secretary of State on Nov. 28. Among other matters these rules allow some relaxation in the restrictions now imposed on the sale of ointments and dressings containing sulphonamides. On and after Jan. 1, 1948, it will be lawful to sell these
without a doctor’s prescription; but, as the ointments are subject to the provisions of section 18 (2) of the Pharmacy and Poisons Act, 1933, their sale must still be entered in the poisons book and the purchaser’s signature obtained. Most dermatologists will regret this step, for it is they who see the disasters which occur from the injudicious use of sulphonamides when employed for topical therapy. The necessity for obtaining the customer’s signature may check sales, but there is a risk that injudicious selfmedication will lead to major and minor catastrophes. In his masterly survey of the use of sulphonamides in dermatology Barberexpressed doubt whether the use of drugs of this series as local applications in superficial infective dermato’ses such as impetigo contagiosa possessed any advantages over rational treatment with older and safer remedies. A similar view was forcibly expressed in the Army Medical Department Bulletin 2 in 1943 when sick-wastage from sulphonamide dermatitis was causing muchconcern. MacKenna 3 has out that local of pointed applications sulphonamides may cause three types of sensitisation-local sensitisation, general sensitisation, and photosensitivity. When local sensitisation occurs, an eczematous reaction with erythema_ and vesicle formation develops at the site of application ; often this is interpreted by the patient as indicating that the original malady is gaining ground, and more vigorous measures may be taken to cure the infection, with disastrous results. General sensitisation is usually accompanied by exacerbation of the local
preparations
’
"
lesions, fever, facial oedema,
severe pruritus, and a rash which may be erythematomacular or vesicular or occasionally bullous. Photosensitivity leads to the development of severe sunburn effects on areas of skin exposed to minimal degrees of sunlight, and this photosensitivity may persist for many weeks. Dermatological literature throughout the world is studded with reports and discussions concerning the hazards of local sulphonamide treatment, but it is agreed that the drugs are used in a large number of cases without ill effect. Hitherto the disasters have been few, though their percentage incidence is not known. Phillips found that among 2430 dermatological patients who passed through the wards of several military hospitals there were 100 cases of sulphonamide dermatitis-an incidence of 4-11%-but we have no knowledge of . the size of the population at risk. Manufacturers will no doubt arrange for the preparations sold to the public to be clearly labelled so that the user is warned never to
generalised
1. Barber, H. W. Practitioner, 1944, 152, 281. 2. 1943, 29, 226. 3. MacKenna. R. M. B. Med. Ann. 1945, p. 307. 4. Phillips, B. Brit. J. Derm. 1946, 58, 213.
650,000) 1098
swabs
in
cases were
pre-immunisation year, there were of diphtheria with 90 deaths, and 13,231 examined of which 2564 were positive. In 1926,
a
1936, when 104,449 persons immunised, there were 48
known to have been of diphtheria with 2 deaths, and 4307 swabs were examined of which 80 were positive. In 1937, surveys of 1774 school-children The figures for in Montreal yielded only 2 carriers. Canadian cities in 1947, ten years later, when they are published, should be conclusive enough to satisfy the most sceptical. AMINO-ACIDS TO
were
cases
INCREASE
PERIPHERAL BLOOD
PROTEINS by virtue of their specific dynamic action are well known to increase heat-production in the body, but there is some doubt whether this increase is accompanied by a rise in the skin temperature of the extremities.7 The specific dynamic action of proteins mainly depends on the presence of a few amino-acids, particularly glycine, alanine, phenylalanine, and tyrosine. Gubner and his colleagues 8 have given glycine in doses of 20 g. by mouth, dissolved in 200-300 ml. of milk, to 25 subjects, some of whom had peripheral vascular disease. In 18 of these the average maximal rise in oxygen consumption above the basal level was 18-4%, but there was a considerable variation in the individual figures and in 4 subjects there was no significant rise in consumption. Skin temperatures were measured in Inormal people and in 4 patients with peripheral vascular disease, and the glycine was found to raise the temperature of toes. and fingers in 3 out of the 4 patients. The rise was greatest in the toes, and the normals showed a rise of 4°C, compared with 2-3°C in the patients. Incases a posterior tibial nerve block was found to have much the same effect as glycine on skin temperature. Glycine produced a significantly greater rise of skin temperature than the ingestion of alcohol. Oscillometric pulsation in the calf was increased after the ingestion of glycine in 8 out of the 11 normal subjects, but in none of the patients with peripheral vascular disease, even though 2 of the patients had significant rises in skin temperature. Blood4. Lancet, 1947, i, 668. 5. Dudley, S. F., May, P. M., O’Flynn, J. A. Spec. Rep. Ser. med. Res. Coun., Lond. 1934, no. 195. 6. McKinnon, N. E., in Control of Common Fevers, London, 1942,
p. 47.
7. 8.
Richards, R. L. Peripheral Circulation in Health and Disease, Edinburgh, 1946, p. 35. Gubner, R., Di Palma, J. R., Moore, E. Amer. J. med. Sci. 1947, 213, 46.
as measured by venous occlusion plethysmography, was increased by glycine, the average rise being 62% in 4 normal subjects, and 30-5% in 4 patients with peripheral vascular disease. This increase is the result of peripheral vasodilatation and increased cardiac output. Much of the early work on peripheral vascular diseases has had to be discarded because of faulty technique, so there is a natural tendency to be cautious in accepting new observations. This investigation, however, seems
flow to the extremities,
to have been well controlled, and if it is confirmed it will undoubtedly stimulate others to explore its practical
applications. RISKS OF LOCAL SULPHONAMIDES THE Home Office has drawn the attention of trade and other organisations to the Poisons (Amendment) Rules, 1947, which were made by the Secretary of State on Nov. 28. Among other matters these rules allow some relaxation in the restrictions now imposed on the sale of ointments and dressings containing sulphonamides. On and after Jan. 1, 1948, it will be lawful to sell these
without a doctor’s prescription; but, as the ointments are subject to the provisions of section 18 (2) of the Pharmacy and Poisons Act, 1933, their sale must still be entered in the poisons book and the purchaser’s signature obtained. Most dermatologists will regret this step, for it is they who see the disasters which occur from the injudicious use of sulphonamides when employed for topical therapy. The necessity for obtaining the customer’s signature may check sales, but there is a risk that injudicious selfmedication will lead to major and minor catastrophes. In his masterly survey of the use of sulphonamides in dermatology Barberexpressed doubt whether the use of drugs of this series as local applications in superficial infective dermato’ses such as impetigo contagiosa possessed any advantages over rational treatment with older and safer remedies. A similar view was forcibly expressed in the Army Medical Department Bulletin 2 in 1943 when sick-wastage from sulphonamide dermatitis was causing muchconcern. MacKenna 3 has out that local of pointed applications sulphonamides may cause three types of sensitisation-local sensitisation, general sensitisation, and photosensitivity. When local sensitisation occurs, an eczematous reaction with erythema_ and vesicle formation develops at the site of application ; often this is interpreted by the patient as indicating that the original malady is gaining ground, and more vigorous measures may be taken to cure the infection, with disastrous results. General sensitisation is usually accompanied by exacerbation of the local
preparations
’
"
lesions, fever, facial oedema,
severe pruritus, and a rash which may be erythematomacular or vesicular or occasionally bullous. Photosensitivity leads to the development of severe sunburn effects on areas of skin exposed to minimal degrees of sunlight, and this photosensitivity may persist for many weeks. Dermatological literature throughout the world is studded with reports and discussions concerning the hazards of local sulphonamide treatment, but it is agreed that the drugs are used in a large number of cases without ill effect. Hitherto the disasters have been few, though their percentage incidence is not known. Phillips found that among 2430 dermatological patients who passed through the wards of several military hospitals there were 100 cases of sulphonamide dermatitis-an incidence of 4-11%-but we have no knowledge of . the size of the population at risk. Manufacturers will no doubt arrange for the preparations sold to the public to be clearly labelled so that the user is warned never to
generalised
1. Barber, H. W. Practitioner, 1944, 152, 281. 2. 1943, 29, 226. 3. MacKenna. R. M. B. Med. Ann. 1945, p. 307. 4. Phillips, B. Brit. J. Derm. 1946, 58, 213.