1045
generally be the cessation of pelvic irradiation.
present aspirin should
given
to
patients onlv after
TABLE 11-ACTIVITY OF FOUR AMINOGI YCOSIDI S ACAINST
98
STRAINS OF
PROVIDFNCIA STl’ARTII
M.R.C. Gastroenterology Unit, Central Middlesex Hospital, Park Royal, London NW10 7NS.
R. E. POUNDER
PROVIDENCIA STUARTII INFECTIONS
SIR,-Recent reports’-3 have focused attention on Prcr! dencia stuartii as a cause of hospital-acquired infection. Significantly, these organisms are usually resistant to4 most commonly used antimicrobials including gentamicin.2 Infections of the urinary and respiratory tracts, wounds, and blood have all been reported. Curreri et al.,5 from a burns unit in Houston, Texas, have documented over a two-year period a rising incidence of infection due to Providencia Stuartii. Providencia pneumonia and bacterxmia occurred with greater frequency than similar infections with Pseudomonas aeruginosa and appeared to be equally lethal in their burned patients. We report here our experience with Providencia stuartii infections over a
three-year period.
All the strains were isolated from clinical material at the central microbiology department, federated Dublin Voluntary Hospitals, over a three-year period ending December, 1974. This laboratory serves six hospitals. Identification was by the TABLE I-SITE OF INFECTION IN
105
PATIENTS WITH PROVIDFNCIA
STUARTII INFECTION
biology, Dudley Road Hospital, Birmingham. The activity of four drugs-kanamycin, gentamicin, tobramycin, and the new aminoglycoside, amikacin-were studied by a routine agarplate dilution method. Oxoid D.S.T. agar and an inoculum of 105 organisms/ml were employed. If a reasonable therapeutic level of kanamycin and amikacin is considered to be 16 mg/1 and of gentamicin and tobramycin 4 mg/1, then only 13.2% and 16.4% of strains can be regarded as sensitive to gentamicin and tobramycin respectively. 76.5% can be regarded as sensitive to kanamycin and 100% sensitive to amikacin. Disc-sensitivity testing was also performed using ampicillin(A), sulphonamide(S), streptomycin(St), cotrimoxazole (Cot), chloramphenicol(Ch) and colistin(Ct) antibiotic discs. 85% were resistant to all these drugs. 1 isolate was sensitive to A, St, S, and Cot; 1 to St and Cot; 1 Cot alone; and 3 to St, S and Cot.
to
S, Cot, and Ct; 2
The high numbers of strains resistant to gentamicin may well be related to the amount of this antibiotic used in our hospitals. We have no precise information on this, but certainly over the last four years this drug has become the antibiotic of choice for serious gram-negative infections. On these results kanamycin is the drug of choice until aminkacin is available. Owing to the specific antibiotic sensitivity, the identification on primary culture is important. We have found that Providencia stuartii on all solid media routinely used has a characteristic odour which is distinct from Proteus species which it resembles in many respects. Central
method of Bascome et al.6 and A.P.I. and Minitek systems. Standard criteria of the clinical significance of the isolates were used.’ Cultures from blood and urine were invariably pure, those from wounds, burns, and sputa frequently mixed. Most patients had had antecedent antimicrobial therapy including gentamicin. Table I shows the number of infected patients for the three-year period according to site. The frequency of isolation increased in the period under study and the total number of patients with infections caused by this organism up to the beginning of September this year equalled the total for 1974. The first 2 cases of septicaemia occurred last year, and both patients were treated blindly with gentamicin after blood-cultures had been taken. The isolates were resistant to this antibiotic and the patients died. Many of the isolates from other sites also appeared to be playing a pathogenic role. To explain the increased isolation-rate the possibility of cross-infection must be entertained. This was probably a factor as there were some instances of clustering. However, most cases appeared unrelated to others. We have found biochemical reactions’ unhelpful when trying to discriminate between cultures of this species and are at present investigating the use of serology and provicine typing in epidemiological investigations. The minimal inhibitory concentration (MIC) of 98 first isolates (7 isolates failed to survive subculture) to aminoglycosides likely to be effective in therapy is shown in table n.These tests were performed in the department of medical micro1. Solberg, C., Matsen, J. M. Am. J. Med. 1971, 50, 241. 2. Overturf, G. D., Wilkins, J., Ressler, R. J. infect Dis. 1974, 129, 353. 3 Klastersky, J., Bogaerts, A. M., Noterman, J., Van Laer, E., Didier, D., Mouawad, E. Scand. J. infect. Dis. 1974, 6, 153. 4. Reynolds, A. V., Hamilton-Miller, J. M. T., Brumfitt, W. Br medJ 1974, iii, 778 5 Curreri, P. W., Bruck, H. M., Lindberg, R. B., Mason, A D., Pruitt, B. A.
Ann. Surg. 1973, 6. Bascome,
177, 133. S., Lapage, S. P., Curtis, M. A., Willcox, W. R. J.
1973, 77, 291.
gen. Microbiol.
to
Microbiology Laboratory, Adelaide Hospital, Dublin
8.
Department of Medical Microbiology, Dudley Road Hospital, Birmingham B18 7QH.
C. T. KEANE L. F. ENGLISH
R. WISE
CONTRACTILE PROTEINS IN EXPERIMENTAL AND HUMAN NEOPLASIA
Six,-The report by Professor Gabbiani and others (Oct. 25, p. 796) of an increase in contractile proteins in human cells confirms
results and conclusions on the rabbit and rat skin carcinomas, examined with smooth-muscle antibody (S.M.A.), immunofluorescent staining of cell outlines in the basal parts of the tumours. Weaker staining was observed in adjacent tumour cells and the most superficial better-differentiated tumour cells were negative. Invasive tumour in the dermis showed the greatest reactivity with S.M.A. In contrast, histologically benign tumours showed less basal staining, and normal epidermal cells were negative. We concluded that the staining reveals cytoplasmic contractile microfilaments, and postulated that they might facilitate local tumour invasion. The less extensive staining observed in benign lesions is in keeping with their limited growth potential. In four human and four experimental rat astrocytomas stained with S.M.A., we observedincreased staining in neoplastic cells as compared with normal astrocytes; we also demon-
cancer
same
our own
topic. We showedl-3 in chemically induced
1. Muller, H. K., Flannery, G. R., Toh, B. H., Kalnins, R Proceedings of Pacific Congress of Dermatology, Sydney, June, 1975; p. 14. 2. Toh, B. H., Muller, H. K. Proceedings of Australian Society for Experimental Pathology, Canberra, August, 1975; p 5. 3. Toh, B. H., Muller, H. K. Cancer Res. (in the press). 4. Toh, B. H., Muller, H. K., Elrick, W. L. Br. J. Cancer, (in the press).
1046 strated filamentous tumour cells.
cytoplasmic staining in individual cultured a
Department of Pathology and Immunology, Monash University Medical School, Melbourne 3181, Australia.
B. H. TOH H. K. MULLER M. N. CAUCHI
INFANTILE SPASMS AND SUBSEQUENT APPEARANCE OF TUBEROUS SCLEROSIS SYNDROME
SIR,-In 1841 The Lancet published a letter from Dr W. J. West’ "on a peculiar form of infantile convulsions". This described an illness in his own son whom he had taken to London for a consultation with Sir Charles Clarke who had already seen four similar cases of what he called "the salaam convulsion". This clinical syndrome is now well recognised and consists of repetitive massive spasms involving the muscles of the neck, trunk, and limbs, either in extension or flexion, each lasting a second or so and occurring in bouts of 10 to 50 or more attacks. Infantile spasms are mostly seen between 6 and 18 months of age and are usually accompanied by regression of motor and mental skills and often by gross multifocal abnormalities (hypsarrhythmia) on the electroencephalogram (E.E.G.). Infantile spasms are a common early manifestation of the tuberous sclerosis syndrome (T.S.S.).2 Such spasms were an early clinical manifestation in thirty-three out of a group of fifty cases in which the full picture of T.s.s. eventually devel-
oped.3 Because the proportion of patients with infantile spasms in whom T.s.s. eventually develops was not known we carried out a survey of all children referred to the Hospital for Sick Children for neurophysiological investigations of possible or probable infantile spasms in the years 1972 and 1973. E.E.G. abnormalities were classified and the clinical notes of these ninety-three patients were scrutinised for confirmation of seizures, the mental defect, skin lesions (poorly pigmented
trunk and limbs, fibroangiomatous lesions of the face often called adenoma sebaceum, shagreen patches), phakoma, intracerebral calcifications, or other evidence ofT.s.s. from neuroradiological investigations. The presence of at least three of the above main clinical features in any child at follow-up was regarded as diagnostic of T.s.s. At referral twenty-five were less than 6 months old, forty-eight were between 6 months and 2 years, and twenty-two were between 2 years and 5 years. Out of ninety-three cases, thirty-nine were excluded either because the history of infantile spasms had not been substantiated (twenty cases) or because in the clinical notes there was no mention of any examination of the skin (twenty-six cases, with an overlap of seven cases). The remaining fifty-four cases all had definite evidence of infantile spasms, skull X-rays had been carried out as well as E.E.G. studies, and the skin had been inspected. Out of this group 85% had mental defect (forty-six cases) and three were doubtfully subnormal. 40% had definite skin changes (twentytwo cases) and nearly 6% (three cases) had intracranial calcifications on X-ray. In this group 26% (fourteen cases) had three or more features undoubtedly diagnostic of T.S.S., while a further 18% (ten further cases) had less obvious but similar features. It seems therefore probable, at least in our material, that amongst those babies presenting with infantile spasms as an early clinical manifestation 2 to 4 years ago, over 25% have already developed various features which are diagnostic of the T.s.s. The above data were collected over a relatively short period, and as the remaining children grow older more obvious diagnostic features of the T.s.s. may vappear in a larger proareas on
portion of cases. 1. West, W J Lancet, 1840/1841, i, 724. Rovere, M, Hoare, R. D., Pampiglione, G. Devl. Med. Child Neurol. 1964, 6, 149. 3. Pampiglione G., Evans, P. R., Harris, R., Moynahan, E. J in Atti delle
2 Della
Conferenze di
aggiornamento
Gaggi); p 73 Bologna, 1968.
Societâ Italiana E.E.G.
(edited by
A.
The following points should be considered in any child with possible history of infantile spasms:
(1) Careful notes should be kept about the precise features of any seizures witnessed by competent observers. If possible further details should be obtained about the sequence of events and the family history. E.E.G. investigations should be carried out at an early phase for consideration of early corticotrophin therapy and repeated at appropriate intervals (preferably 10 and 30 days after starting the drug, as well as 6, 12, 24 months later to check on progress). (2) The skin should be carefully inspected for poorly pigmented areas during infancy, while in older children facial fibroangiomatous lesions (adenoma sebaceum) should not be missed: differentiation from acne may be difficult during adolescence and the two conditions may coexist. In case of doubt the opinion of a dermatologist interested m the field should be sought, remembering that the absence as well as the presence of such lesions should be noted. (3) Ophthalmoscopic examinations should be repeated every few years. (4) In infancy a single skull X-ray rarely reveals intracranial calcifications ofr.s.s., while after the age of 2-4 years the chances increase. If possible therefore skull X-rays should be repeated at the age of 6-12 years. (5) Any post-mortem examination may be of very limited value unless the brain is studied by an interested neuropathologist prepared to carry out detailed histological studies. We wish to draw attention to the complex evolution of these clinical phenomena which have important prognostic and genetic implications and we would be pleased to learn from our colleagues about their experience with similar cases. Department of Neurophysiology, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH.
G. PAMPIGLIONE E. PUGH
THYROTOXICOSIS ASSOCIATED WITH SPLENIC ATROPHY
SIR,-We noted with interest that 2 of the 12 patients with
splenic atrophy described by Dr Wardrop and his colleagues (July 5, p. 4) also had thyrotoxicosis. Although the association of splenic atrophy with coeliac disease is well recognised,’ the association with thyrotoxicosis is poorly documented.2 We report 3 more cases of thyrotoxicosis associated with splenic atrophy. Case 1.-A 54-year-old woman with a history of goitre since girlhood first presented with thyrotoxicosis and severe bilateral exophthalmos in 1963. In 1968 she was referred because of inadequate antithyroid-drug control of her thyrotoxicosis. Serum-thyroxine was greater than 20g/dl (normal 5-5-ll-5[ig/dl), free-thyroxine index greater than 30 (normal 4-14), antithyroglobulin antibody (haemagglutination and latex slide test) positive, long-acting thyroid stimulator (L.A.T.S.) negative (kindly performed by Dr D. D. Adams). She had bilateral infiltrative ophthalmopathy, a moderate-sized diffusely enlarged thyroid, and pallor. The hsemaglobin was 6g/dl, and the blood-film showed anisocytosis, poikilocytosis, target cells, Microspherocytes, and scanty Howell-Jolly bodies. The bone-marrow showed a lack of iron stores with a normoblastic hyperplastic picture. Serumiron was 8µg/dl (normal 55-190µg/dl), serum-iron-binding capacity was 384g/dl (normal 250-420jjtg/dl), serum-folate 2.2ng/ml (normal 7-16ng/ml). Serum vitamin B12, calcium, and carotene were normal, as were the D-xylose-absorption test and fsecal-fat excretion. Banummeal and follow-through-enema examinations were normal. The anaemia responded to parenteral and oral iron therapy. Later studies including a 99’"Tc-sulphur-colloid scan and chromium-51heat- damaged red cell studies confirmed splenic atrophy. The thyrotoxicosis was permanently controlled with 5mCi iodine-131 administered in June, 1968. Case 2.-A 43-year-old woman presented in April, 1975, with moderately severe thyrotoxicosis, total serum-thyroxine l!’6d! (normal 3-5-lOjjtg/dI), free-thyroxine index greater than 30 (normal
4-12), antithyroglobulin-haemagglutination test positive, thyroid-antimicrosomal-immunofluorescent-antibody negative. A moderately enlarged diffuse goitre was present, and there was no significant ophthalmopathy. She was not antmic (haemaglobin 12.1g/dl), but a blood-film showed anisocytosis with target cells and some Howell-Jolly 1. 2.
K. T., Read, A. E. Gut, 1966, 7, 140 1908, 58, 441.
McCarthy, C. F., Fraser, I. D., Evan, Schur,
H. Wien. med. Wschr.
generally be the cessation of pelvic irradiation.
present aspirin should
given
to
patients onlv after
TABLE 11-ACTIVITY OF FOUR AMINOGI YCOSIDI S ACAINST
98
STRAINS OF
PROVIDFNCIA STl’ARTII
M.R.C. Gastroenterology Unit, Central Middlesex Hospital, Park Royal, London NW10 7NS.
R. E. POUNDER
PROVIDENCIA STUARTII INFECTIONS
SIR,-Recent reports’-3 have focused attention on Prcr! dencia stuartii as a cause of hospital-acquired infection. Significantly, these organisms are usually resistant to4 most commonly used antimicrobials including gentamicin.2 Infections of the urinary and respiratory tracts, wounds, and blood have all been reported. Curreri et al.,5 from a burns unit in Houston, Texas, have documented over a two-year period a rising incidence of infection due to Providencia Stuartii. Providencia pneumonia and bacterxmia occurred with greater frequency than similar infections with Pseudomonas aeruginosa and appeared to be equally lethal in their burned patients. We report here our experience with Providencia stuartii infections over a
three-year period.
All the strains were isolated from clinical material at the central microbiology department, federated Dublin Voluntary Hospitals, over a three-year period ending December, 1974. This laboratory serves six hospitals. Identification was by the TABLE I-SITE OF INFECTION IN
105
PATIENTS WITH PROVIDFNCIA
STUARTII INFECTION
biology, Dudley Road Hospital, Birmingham. The activity of four drugs-kanamycin, gentamicin, tobramycin, and the new aminoglycoside, amikacin-were studied by a routine agarplate dilution method. Oxoid D.S.T. agar and an inoculum of 105 organisms/ml were employed. If a reasonable therapeutic level of kanamycin and amikacin is considered to be 16 mg/1 and of gentamicin and tobramycin 4 mg/1, then only 13.2% and 16.4% of strains can be regarded as sensitive to gentamicin and tobramycin respectively. 76.5% can be regarded as sensitive to kanamycin and 100% sensitive to amikacin. Disc-sensitivity testing was also performed using ampicillin(A), sulphonamide(S), streptomycin(St), cotrimoxazole (Cot), chloramphenicol(Ch) and colistin(Ct) antibiotic discs. 85% were resistant to all these drugs. 1 isolate was sensitive to A, St, S, and Cot; 1 to St and Cot; 1 Cot alone; and 3 to St, S and Cot.
to
S, Cot, and Ct; 2
The high numbers of strains resistant to gentamicin may well be related to the amount of this antibiotic used in our hospitals. We have no precise information on this, but certainly over the last four years this drug has become the antibiotic of choice for serious gram-negative infections. On these results kanamycin is the drug of choice until aminkacin is available. Owing to the specific antibiotic sensitivity, the identification on primary culture is important. We have found that Providencia stuartii on all solid media routinely used has a characteristic odour which is distinct from Proteus species which it resembles in many respects. Central
method of Bascome et al.6 and A.P.I. and Minitek systems. Standard criteria of the clinical significance of the isolates were used.’ Cultures from blood and urine were invariably pure, those from wounds, burns, and sputa frequently mixed. Most patients had had antecedent antimicrobial therapy including gentamicin. Table I shows the number of infected patients for the three-year period according to site. The frequency of isolation increased in the period under study and the total number of patients with infections caused by this organism up to the beginning of September this year equalled the total for 1974. The first 2 cases of septicaemia occurred last year, and both patients were treated blindly with gentamicin after blood-cultures had been taken. The isolates were resistant to this antibiotic and the patients died. Many of the isolates from other sites also appeared to be playing a pathogenic role. To explain the increased isolation-rate the possibility of cross-infection must be entertained. This was probably a factor as there were some instances of clustering. However, most cases appeared unrelated to others. We have found biochemical reactions’ unhelpful when trying to discriminate between cultures of this species and are at present investigating the use of serology and provicine typing in epidemiological investigations. The minimal inhibitory concentration (MIC) of 98 first isolates (7 isolates failed to survive subculture) to aminoglycosides likely to be effective in therapy is shown in table n.These tests were performed in the department of medical micro1. Solberg, C., Matsen, J. M. Am. J. Med. 1971, 50, 241. 2. Overturf, G. D., Wilkins, J., Ressler, R. J. infect Dis. 1974, 129, 353. 3 Klastersky, J., Bogaerts, A. M., Noterman, J., Van Laer, E., Didier, D., Mouawad, E. Scand. J. infect. Dis. 1974, 6, 153. 4. Reynolds, A. V., Hamilton-Miller, J. M. T., Brumfitt, W. Br medJ 1974, iii, 778 5 Curreri, P. W., Bruck, H. M., Lindberg, R. B., Mason, A D., Pruitt, B. A.
Ann. Surg. 1973, 6. Bascome,
177, 133. S., Lapage, S. P., Curtis, M. A., Willcox, W. R. J.
1973, 77, 291.
gen. Microbiol.
to
Microbiology Laboratory, Adelaide Hospital, Dublin
8.
Department of Medical Microbiology, Dudley Road Hospital, Birmingham B18 7QH.
C. T. KEANE L. F. ENGLISH
R. WISE
CONTRACTILE PROTEINS IN EXPERIMENTAL AND HUMAN NEOPLASIA
Six,-The report by Professor Gabbiani and others (Oct. 25, p. 796) of an increase in contractile proteins in human cells confirms
results and conclusions on the rabbit and rat skin carcinomas, examined with smooth-muscle antibody (S.M.A.), immunofluorescent staining of cell outlines in the basal parts of the tumours. Weaker staining was observed in adjacent tumour cells and the most superficial better-differentiated tumour cells were negative. Invasive tumour in the dermis showed the greatest reactivity with S.M.A. In contrast, histologically benign tumours showed less basal staining, and normal epidermal cells were negative. We concluded that the staining reveals cytoplasmic contractile microfilaments, and postulated that they might facilitate local tumour invasion. The less extensive staining observed in benign lesions is in keeping with their limited growth potential. In four human and four experimental rat astrocytomas stained with S.M.A., we observedincreased staining in neoplastic cells as compared with normal astrocytes; we also demon-
cancer
same
our own
topic. We showedl-3 in chemically induced
1. Muller, H. K., Flannery, G. R., Toh, B. H., Kalnins, R Proceedings of Pacific Congress of Dermatology, Sydney, June, 1975; p. 14. 2. Toh, B. H., Muller, H. K. Proceedings of Australian Society for Experimental Pathology, Canberra, August, 1975; p 5. 3. Toh, B. H., Muller, H. K. Cancer Res. (in the press). 4. Toh, B. H., Muller, H. K., Elrick, W. L. Br. J. Cancer, (in the press).
1046 strated filamentous tumour cells.
cytoplasmic staining in individual cultured a
Department of Pathology and Immunology, Monash University Medical School, Melbourne 3181, Australia.
B. H. TOH H. K. MULLER M. N. CAUCHI
INFANTILE SPASMS AND SUBSEQUENT APPEARANCE OF TUBEROUS SCLEROSIS SYNDROME
SIR,-In 1841 The Lancet published a letter from Dr W. J. West’ "on a peculiar form of infantile convulsions". This described an illness in his own son whom he had taken to London for a consultation with Sir Charles Clarke who had already seen four similar cases of what he called "the salaam convulsion". This clinical syndrome is now well recognised and consists of repetitive massive spasms involving the muscles of the neck, trunk, and limbs, either in extension or flexion, each lasting a second or so and occurring in bouts of 10 to 50 or more attacks. Infantile spasms are mostly seen between 6 and 18 months of age and are usually accompanied by regression of motor and mental skills and often by gross multifocal abnormalities (hypsarrhythmia) on the electroencephalogram (E.E.G.). Infantile spasms are a common early manifestation of the tuberous sclerosis syndrome (T.S.S.).2 Such spasms were an early clinical manifestation in thirty-three out of a group of fifty cases in which the full picture of T.s.s. eventually devel-
oped.3 Because the proportion of patients with infantile spasms in whom T.s.s. eventually develops was not known we carried out a survey of all children referred to the Hospital for Sick Children for neurophysiological investigations of possible or probable infantile spasms in the years 1972 and 1973. E.E.G. abnormalities were classified and the clinical notes of these ninety-three patients were scrutinised for confirmation of seizures, the mental defect, skin lesions (poorly pigmented
trunk and limbs, fibroangiomatous lesions of the face often called adenoma sebaceum, shagreen patches), phakoma, intracerebral calcifications, or other evidence ofT.s.s. from neuroradiological investigations. The presence of at least three of the above main clinical features in any child at follow-up was regarded as diagnostic of T.s.s. At referral twenty-five were less than 6 months old, forty-eight were between 6 months and 2 years, and twenty-two were between 2 years and 5 years. Out of ninety-three cases, thirty-nine were excluded either because the history of infantile spasms had not been substantiated (twenty cases) or because in the clinical notes there was no mention of any examination of the skin (twenty-six cases, with an overlap of seven cases). The remaining fifty-four cases all had definite evidence of infantile spasms, skull X-rays had been carried out as well as E.E.G. studies, and the skin had been inspected. Out of this group 85% had mental defect (forty-six cases) and three were doubtfully subnormal. 40% had definite skin changes (twentytwo cases) and nearly 6% (three cases) had intracranial calcifications on X-ray. In this group 26% (fourteen cases) had three or more features undoubtedly diagnostic of T.S.S., while a further 18% (ten further cases) had less obvious but similar features. It seems therefore probable, at least in our material, that amongst those babies presenting with infantile spasms as an early clinical manifestation 2 to 4 years ago, over 25% have already developed various features which are diagnostic of the T.s.s. The above data were collected over a relatively short period, and as the remaining children grow older more obvious diagnostic features of the T.s.s. may vappear in a larger proareas on
portion of cases. 1. West, W J Lancet, 1840/1841, i, 724. Rovere, M, Hoare, R. D., Pampiglione, G. Devl. Med. Child Neurol. 1964, 6, 149. 3. Pampiglione G., Evans, P. R., Harris, R., Moynahan, E. J in Atti delle
2 Della
Conferenze di
aggiornamento
Gaggi); p 73 Bologna, 1968.
Societâ Italiana E.E.G.
(edited by
A.
The following points should be considered in any child with possible history of infantile spasms:
(1) Careful notes should be kept about the precise features of any seizures witnessed by competent observers. If possible further details should be obtained about the sequence of events and the family history. E.E.G. investigations should be carried out at an early phase for consideration of early corticotrophin therapy and repeated at appropriate intervals (preferably 10 and 30 days after starting the drug, as well as 6, 12, 24 months later to check on progress). (2) The skin should be carefully inspected for poorly pigmented areas during infancy, while in older children facial fibroangiomatous lesions (adenoma sebaceum) should not be missed: differentiation from acne may be difficult during adolescence and the two conditions may coexist. In case of doubt the opinion of a dermatologist interested m the field should be sought, remembering that the absence as well as the presence of such lesions should be noted. (3) Ophthalmoscopic examinations should be repeated every few years. (4) In infancy a single skull X-ray rarely reveals intracranial calcifications ofr.s.s., while after the age of 2-4 years the chances increase. If possible therefore skull X-rays should be repeated at the age of 6-12 years. (5) Any post-mortem examination may be of very limited value unless the brain is studied by an interested neuropathologist prepared to carry out detailed histological studies. We wish to draw attention to the complex evolution of these clinical phenomena which have important prognostic and genetic implications and we would be pleased to learn from our colleagues about their experience with similar cases. Department of Neurophysiology, Hospital for Sick Children, Great Ormond Street, London WC1N 3JH.
G. PAMPIGLIONE E. PUGH
THYROTOXICOSIS ASSOCIATED WITH SPLENIC ATROPHY
SIR,-We noted with interest that 2 of the 12 patients with
splenic atrophy described by Dr Wardrop and his colleagues (July 5, p. 4) also had thyrotoxicosis. Although the association of splenic atrophy with coeliac disease is well recognised,’ the association with thyrotoxicosis is poorly documented.2 We report 3 more cases of thyrotoxicosis associated with splenic atrophy. Case 1.-A 54-year-old woman with a history of goitre since girlhood first presented with thyrotoxicosis and severe bilateral exophthalmos in 1963. In 1968 she was referred because of inadequate antithyroid-drug control of her thyrotoxicosis. Serum-thyroxine was greater than 20g/dl (normal 5-5-ll-5[ig/dl), free-thyroxine index greater than 30 (normal 4-14), antithyroglobulin antibody (haemagglutination and latex slide test) positive, long-acting thyroid stimulator (L.A.T.S.) negative (kindly performed by Dr D. D. Adams). She had bilateral infiltrative ophthalmopathy, a moderate-sized diffusely enlarged thyroid, and pallor. The hsemaglobin was 6g/dl, and the blood-film showed anisocytosis, poikilocytosis, target cells, Microspherocytes, and scanty Howell-Jolly bodies. The bone-marrow showed a lack of iron stores with a normoblastic hyperplastic picture. Serumiron was 8µg/dl (normal 55-190µg/dl), serum-iron-binding capacity was 384g/dl (normal 250-420jjtg/dl), serum-folate 2.2ng/ml (normal 7-16ng/ml). Serum vitamin B12, calcium, and carotene were normal, as were the D-xylose-absorption test and fsecal-fat excretion. Banummeal and follow-through-enema examinations were normal. The anaemia responded to parenteral and oral iron therapy. Later studies including a 99’"Tc-sulphur-colloid scan and chromium-51heat- damaged red cell studies confirmed splenic atrophy. The thyrotoxicosis was permanently controlled with 5mCi iodine-131 administered in June, 1968. Case 2.-A 43-year-old woman presented in April, 1975, with moderately severe thyrotoxicosis, total serum-thyroxine l!’6d! (normal 3-5-lOjjtg/dI), free-thyroxine index greater than 30 (normal
4-12), antithyroglobulin-haemagglutination test positive, thyroid-antimicrosomal-immunofluorescent-antibody negative. A moderately enlarged diffuse goitre was present, and there was no significant ophthalmopathy. She was not antmic (haemaglobin 12.1g/dl), but a blood-film showed anisocytosis with target cells and some Howell-Jolly 1. 2.
K. T., Read, A. E. Gut, 1966, 7, 140 1908, 58, 441.
McCarthy, C. F., Fraser, I. D., Evan, Schur,
H. Wien. med. Wschr.
