108 From the first days of treatment, both children felt better and showed increasing activity. There was immediate and regular growth acceleration (table n) but liver size and metabolic disturbances remained unchanged (table i). Appetite was unaffected but intake and output has not been studied. The growth spurt may be questionably dependent on sex maturation in patient 1. Variations in his plasma luteinisinghormone and follicle-stimulating hormone concentrations before and after injection of luteinising-hormone-releasinghormone showed that puberty began with apparent ossification of sesamoid on the 7th month of treatment. However, the absence of increase in gonadotropin secretion after stimulation in patient 2 suggests that the growth acceleration is more specifically associated with the treatment. These results suggest that growth retardation in glycogenstorage disease may be related to peripheral hypoinsulinism. Insulin itself appears to promote growth’ and this effect may explain the accelerated growth in stature associated with hyperinsulinism, as in infants of diabetic mothers, Beckwith’s syndrome, and congenital total lipodystrophy. The mechanisms of this action remains unknown. The subnormal plasma somatomedin activity in patient 2 was not modified by the treatment. The treatment of although not without risks, may
disease with insulin, thus be valuable when growth retardation is the main complaint and has the advantage that it can be interrupted at any time.
glycogen-storage
Unité de Recherche d’Hépatologie Infantile INSERM U and Clinique de Pédiatrie, Université Paris-Sud,
56,
Hôpital d’Enfants,
O. DULAC M. ODIÈVRE
94270 Bicêtre, France
D, ALAGILLE
DISTURBED "FLIGHT OF COLOURS" IN MULTIPLE SCLEROSIS
SIR,-There has lately been a lot of interest in subclinical disturbances of the central nervous system of patients with multiple sclerosis (M.S.) which are detectable by electrophysiological tests (registration of eye-movements, orbicularis oculi reflex, bladder function and evoked potentials, especially the visual evoked responses). Detection of these subclinical lesions is expected to become an important diagnostic aid in mt.s. We feel that "the flight-of-colours" test can be used as a very simple clinical method to detect subclinical lesions of the visual system. This test was found to be abnormal when any lesion of the visual system, including retrobulbar neuritis, involved the central vision.’ The test often did not return to normal in M.S. patients recovering from retrobulbar neuritis.2 We studied this test in 50 patients with definite M.S. using methods and criteria given by Feldman et al.’ The subject is placed in a dimly lit room and after about 5 min adaptation light from a bright pocket torch is directed into one eye for 10 s while the other eye is covered or closed. After the illumination the patient closes both eyes and reports the after-image colours he is seeing for at least 3 min. Both eyes are investigated more than once with an interval between tests. In this test the first response should not be considered as significant. The responses are judged by the number of colour changes, the duration and intensity of each colour phase as well as the rate of change and the total duration of after-images in time. A normal response consists of many colour changes, many different colours, rapidly changing colours and a duration of at least 1-Lmin. Responses are considered to be abnormal when only a few colour changes are seen for about 1 min or less. Some experience with this test in normal persons is recommended before testing patients.
We found normal responses in 24 normal controls and 18 of patients with neurological diseases other than mt.s. who had no visual symptoms. The exception was a patient recovering from a brain concussion. 37 of 50 M.S. patients (74%) had a disturbed flight of colours, 10 having a deficient response in 1 eye, 27 in both eyes. 11 patients had visual signs or symptoms in clinical examination, 5 of whom had an abnormal response in 1 eye and 6 in both eyes. 26 patients (52%) had abnormal responses without clinical visual signs or symptoms, 6 of whom had an abnormal response in 1 eye, and 20 in both eyes; only 7 of them had a history of retrobulbar neuritis. The remaining 13 M.S. patients, in whom visual signs were absent, had normal responses. The part of the visual system affected in this disturbed flight of colours is unknown. It is tempting to assume a subclinical retrobulbar neuritis but the mostly bilateral disturbances make this questionable. In theory any part of the central nervous system with a role in central vision can be involved.
19
Kliniek
Feldman, L., Todman, L., Bender, B. J. Neurol. Neurosurg. Psychiat. 1974, 37, 1265. 2. Todman, L. Unpublished.
C. A. VAN DONSELAAR J. M. MINDERHOUD
SERUM-CHORIONIC-GONADOTROPIN IN NORMAL AND ECTOPIC PREGNANCY
SiR,—The advent of simple, sensitive, and specific radio-
ligand assays for human chorionic gonadotropin (H.c.G.) has permitted analysis of serum from women with suspected extrauterine pregnancy to be a routine test. In this condition the signs and symptoms resemble those of salpingitis and ovulation bleeding. Laparoscopy or observation in hospital could often be avoided if H.C.G. analysis were able to exclude normal or ectopic pregnancy. It has been claimedl,2 that measurement 1. Kosasa, T. S., Taymor, M. L., Goldstein, D. P., Levesque, L. A. Obstet. Gynec. 1973, 42, 868. 2. Saxena, B. B., Landesman, R. Fertil. Steril. 1975, 26, 397.
weeks after last menstrual Serum-H.C.G. in patients (squares) and intrauterine come
1.
J. MOURIK
Neurologie, Rijksuniversitiet, Groningen, Netherlands voor
with
period
extrauterine pregnancy with a normal out-
pregnancies
(circles).
The filled circles refer to patients first suspected of having an extrauterine pregnancy; open circles refer to normal pregnant women.
109 of H.C.G. is also useful for the differentiation between intrauterine and extrauterine pregnancy, abnormally low values being found in ectopic pregnancies. We measured serum-H.C.G. in patients with suspected extrauterine pregnancy over a six-month period, ending in March, 1977. The method (C.I.S., Institut National des RadlOéléments, Fleurus, Belgium) is virtually unaffected by lutellllsing hormone and has low reactivity with H.C.G. subunits. 14 patients had extrauterine pregnancies and 13 had intrauterine pregnancies with normal outcome. 7 pregnancies ended in spontaneous abortion. Of the 145 patients, 111 turned out not to be pregnant. As shown in the figure, which includes results from 17 additional women with asymptomatic normal pregnancies, most of the patients with extrauterine pregnancies had H.C.G. concentrations indistinguishable from those of normal pregnancies. Thus a single H.c.G. analysis could not discriminate between intrauterine and ectopic pregnancies, although a low value in relation to the time of gestation could strengthen a suspicion of ectopic pregnancy. From these findings and the fact that gestational age is difficult to determine in cases of ectopic pregnancy we conclude that the H.c.G. assay has limitations in the differentiation of normal and ectopic pregnancies. The real advantage of the analysis was that pregnancy could be excluded in 111 of 145 patients so that the patient could leave hospital if her clinical situation so permitted. Departments of Clinical Chemistry and Obstetrics and Gynæcology, University of Gothenburg, Sahlgren’s Hospital, S-413 45 Gothenburg, Sweden
GÖRAN LINDSTEDT PER-ARNE LUNDBERG LENNART ENK LARS REDVALL
ARYL HYDROCARBON HYDROXYLASE INDUCIBILITY AND CARCINOMA OF ORAL CAVITY
SIR,-High aryl hydrocarbon hydroxylase (A.H.H.) inducibility seems to be over-represented in smoke-induced respiratorysuch as lung’ and laryngeal2 carcinoma. Howof carcinoma of the urinary bladder, which is also related to smoking,3,4 Kellerman et al. found no overrepresentation of high A.H.H. inducibility. We have confirmed this in 46 further cases of carcinoma of the urinary bladder (unpublished) and in 30 cases of cancers of the urinary pelvis and ureter.5 Even though aromatic amines rather than polycyclic aromatic hydrocarbons may be involved in urothelial carcinogenesis,6 A.H.H. might also affect the metabolism of arylamines.7 A consistent difference in A.H.H. inducibility pattern between smoke-related urothelial and respiratory-tract carcinomas would seem to be of considerable interest. We report here our results on A.H.H. inducibility assessments in carcinoma of the oral cavity. In the period 1966-76, 77 cases of squamous cell, oral, oropharyngeal, and epipharyngeal carcinomas were clinically diagnosed and histopathologically verified at the department of otorhinolaryngology, Malmö General Hospital. In the autumn of 1976, 50 were still alive, and all who were below eighty years of age (44) were invited to the section of preventive medicine, Malmö General Hospital, for A.H.H. assessment. 34 patients (13 gingival, 7 lingual, 5 epipharyngeal, 2 palatal, 5 other oral sites, 2 advanced leukoplakias), left venous blood-samples which were assessed for A.H.H. inducibility2 at the the department of tumour cytogenetics, Wallenberg Laboratory, Lund. tract cancers
ever, in 12
cases
A.H.H.
DISTRIBUTION*
AND NUMBER OF SMOKERS AND
NON-SMOKERS
*Expected numbers calculated from data of Kellerman et al.’ Male/female ratios shown in parentheses.
Hereditary, occupational, and smoking histories were obtained from all patients. The main results are summarised in the table. In the males (28 smokers, 1 non-smoker) but not in the females (3 smokers, 2 non-smokers), there was an over-representation of tobacco consumers. 3 of the men were asphalt workers. Occupational and family histories were otherwise unremarkable. There was a highly significant over-representation of high A.H.H. inducibility in the material. Although oral carcinomas form a heterogeneous group, we included only squamous-cell varieties, which have been shown to be clearly associated with smoking.8 The pattern in oral carcinoma seems similar to the over-representation of high A.H.H. inducibility found in smokedependent pulmonary’ and laryngeaP carcinomas, and supports the concept that A.H.H. plays an important role in the activation of carcinogens in various smoke-related airway tract cancers; this does not seem to apply in urothelial carcinogenesis. Section of Preventive Medicine and Departments of Internal Medicine and
Oto-Rhino-Laryngology, University of Lund, Hospital,
Malmö General
Malmö, Sweden; Research Department I and Department of Lung Medicine, University Hospital, Lund: and Department of Tumour Cytogenetics,
Wallenberg Laboratory, University of Lund
E. TRELL R. KORSGAARD P. KITZING K. LUNDGREN I. MATTIASSON
CROHN’S DISEASE RESPONDING TO ORAL DISODIUM CROMOGLYCATE
SIR,-A 25-year-old male presented in January, 1977, with 3-year history of weight loss, vague abdominal pain, and intermittent diarrhoea containing blood and mucus. Rectal a
biopsy and barium enema showd a mild non-specific proctitis. His haemoglobin was 10-0 g/dl, erythrocyte-sedimentation rate (E.S.R.) 51 mm/h, and serum-albumin 23 g/1. Ulcerative colitis was diagnosed and salazopyrine and steroid enemas were started. However, he did not respond satisfactorily and was admitted to hospital where he was transfused and given highdose oral steroids. His general health improved and the E.S.R. fell to 3 mm/h, but he did not gain weight, his diarrhoea persisted, and his serum-albumin remained low. A barium follow-
through disclosed extensive small-bowel Crohn’s disease. He was discharged on 30 mg prednisone daily, and during outpatient follow-up his weight slowly increased, his diarrhoea improved, and his serum-albumin rose to normal. His oral steroids were gradually reduced, but, though his haemoglobin and serum-albumin concentrations remained satisfactory, his E.S.R. 45 mm/h and he had severe clinical exacerbation unresoral metronidazole. He had to be admitted to hospital, where he was put on an elemental diet (’Vivonex’) and highdose oral steroids. Rectal biopsy confirmed Crohn’s disease. He did not improve and after a week a tender, indurated mass was noted in the right iliac fossa. Surgery was thought necessary, and while awaiting this, the patient was given oral disodium rose to
Kellerman, G., Shaw, C. R., Lyten-Kellerman, M. New Engl. J. Med. 1973, 289, 934. 2. Trell, E., Korsgaard, R., Hood, B., Kitzing, P., Nordén, G., Simonsson, B. G. Lancet, 1976, ii, 140. 3. Lilienfeld, A. M., Levin, M. L., Moore, G. E. Archs intern. Med. 1956, 98, 129. 4. Hammon, E. C., Horn, D.J. Am. med. Ass., 1958, 166, 294. 5. Trell, E., Oldbring, J., Korsgaard, R., Mattiasson, I. Lancet, 1977, ii, 612. 6. Kerr, W. K., Barkin, M., Levers, P. E., Woo, s.K-C., Menczyk, A. R. T. Can. med. Ass. J., 1965, 93, 1. 7 Miller, J. A., Miller, E. C. J. natn. Cancer Inst. 1971, 47, V.
ponsive
8.
Auerbach, O., 253.
Stout, A. P., Hammon, E. C. New Engl. J. Med. 1961, 265,
disease with insulin, thus be valuable when growth retardation is the main complaint and has the advantage that it can be interrupted at any time.
glycogen-storage
Unité de Recherche d’Hépatologie Infantile INSERM U and Clinique de Pédiatrie, Université Paris-Sud,
56,
Hôpital d’Enfants,
O. DULAC M. ODIÈVRE
94270 Bicêtre, France
D, ALAGILLE
DISTURBED "FLIGHT OF COLOURS" IN MULTIPLE SCLEROSIS
SIR,-There has lately been a lot of interest in subclinical disturbances of the central nervous system of patients with multiple sclerosis (M.S.) which are detectable by electrophysiological tests (registration of eye-movements, orbicularis oculi reflex, bladder function and evoked potentials, especially the visual evoked responses). Detection of these subclinical lesions is expected to become an important diagnostic aid in mt.s. We feel that "the flight-of-colours" test can be used as a very simple clinical method to detect subclinical lesions of the visual system. This test was found to be abnormal when any lesion of the visual system, including retrobulbar neuritis, involved the central vision.’ The test often did not return to normal in M.S. patients recovering from retrobulbar neuritis.2 We studied this test in 50 patients with definite M.S. using methods and criteria given by Feldman et al.’ The subject is placed in a dimly lit room and after about 5 min adaptation light from a bright pocket torch is directed into one eye for 10 s while the other eye is covered or closed. After the illumination the patient closes both eyes and reports the after-image colours he is seeing for at least 3 min. Both eyes are investigated more than once with an interval between tests. In this test the first response should not be considered as significant. The responses are judged by the number of colour changes, the duration and intensity of each colour phase as well as the rate of change and the total duration of after-images in time. A normal response consists of many colour changes, many different colours, rapidly changing colours and a duration of at least 1-Lmin. Responses are considered to be abnormal when only a few colour changes are seen for about 1 min or less. Some experience with this test in normal persons is recommended before testing patients.
We found normal responses in 24 normal controls and 18 of patients with neurological diseases other than mt.s. who had no visual symptoms. The exception was a patient recovering from a brain concussion. 37 of 50 M.S. patients (74%) had a disturbed flight of colours, 10 having a deficient response in 1 eye, 27 in both eyes. 11 patients had visual signs or symptoms in clinical examination, 5 of whom had an abnormal response in 1 eye and 6 in both eyes. 26 patients (52%) had abnormal responses without clinical visual signs or symptoms, 6 of whom had an abnormal response in 1 eye, and 20 in both eyes; only 7 of them had a history of retrobulbar neuritis. The remaining 13 M.S. patients, in whom visual signs were absent, had normal responses. The part of the visual system affected in this disturbed flight of colours is unknown. It is tempting to assume a subclinical retrobulbar neuritis but the mostly bilateral disturbances make this questionable. In theory any part of the central nervous system with a role in central vision can be involved.
19
Kliniek
Feldman, L., Todman, L., Bender, B. J. Neurol. Neurosurg. Psychiat. 1974, 37, 1265. 2. Todman, L. Unpublished.
C. A. VAN DONSELAAR J. M. MINDERHOUD
SERUM-CHORIONIC-GONADOTROPIN IN NORMAL AND ECTOPIC PREGNANCY
SiR,—The advent of simple, sensitive, and specific radio-
ligand assays for human chorionic gonadotropin (H.c.G.) has permitted analysis of serum from women with suspected extrauterine pregnancy to be a routine test. In this condition the signs and symptoms resemble those of salpingitis and ovulation bleeding. Laparoscopy or observation in hospital could often be avoided if H.C.G. analysis were able to exclude normal or ectopic pregnancy. It has been claimedl,2 that measurement 1. Kosasa, T. S., Taymor, M. L., Goldstein, D. P., Levesque, L. A. Obstet. Gynec. 1973, 42, 868. 2. Saxena, B. B., Landesman, R. Fertil. Steril. 1975, 26, 397.
weeks after last menstrual Serum-H.C.G. in patients (squares) and intrauterine come
1.
J. MOURIK
Neurologie, Rijksuniversitiet, Groningen, Netherlands voor
with
period
extrauterine pregnancy with a normal out-
pregnancies
(circles).
The filled circles refer to patients first suspected of having an extrauterine pregnancy; open circles refer to normal pregnant women.
109 of H.C.G. is also useful for the differentiation between intrauterine and extrauterine pregnancy, abnormally low values being found in ectopic pregnancies. We measured serum-H.C.G. in patients with suspected extrauterine pregnancy over a six-month period, ending in March, 1977. The method (C.I.S., Institut National des RadlOéléments, Fleurus, Belgium) is virtually unaffected by lutellllsing hormone and has low reactivity with H.C.G. subunits. 14 patients had extrauterine pregnancies and 13 had intrauterine pregnancies with normal outcome. 7 pregnancies ended in spontaneous abortion. Of the 145 patients, 111 turned out not to be pregnant. As shown in the figure, which includes results from 17 additional women with asymptomatic normal pregnancies, most of the patients with extrauterine pregnancies had H.C.G. concentrations indistinguishable from those of normal pregnancies. Thus a single H.c.G. analysis could not discriminate between intrauterine and ectopic pregnancies, although a low value in relation to the time of gestation could strengthen a suspicion of ectopic pregnancy. From these findings and the fact that gestational age is difficult to determine in cases of ectopic pregnancy we conclude that the H.c.G. assay has limitations in the differentiation of normal and ectopic pregnancies. The real advantage of the analysis was that pregnancy could be excluded in 111 of 145 patients so that the patient could leave hospital if her clinical situation so permitted. Departments of Clinical Chemistry and Obstetrics and Gynæcology, University of Gothenburg, Sahlgren’s Hospital, S-413 45 Gothenburg, Sweden
GÖRAN LINDSTEDT PER-ARNE LUNDBERG LENNART ENK LARS REDVALL
ARYL HYDROCARBON HYDROXYLASE INDUCIBILITY AND CARCINOMA OF ORAL CAVITY
SIR,-High aryl hydrocarbon hydroxylase (A.H.H.) inducibility seems to be over-represented in smoke-induced respiratorysuch as lung’ and laryngeal2 carcinoma. Howof carcinoma of the urinary bladder, which is also related to smoking,3,4 Kellerman et al. found no overrepresentation of high A.H.H. inducibility. We have confirmed this in 46 further cases of carcinoma of the urinary bladder (unpublished) and in 30 cases of cancers of the urinary pelvis and ureter.5 Even though aromatic amines rather than polycyclic aromatic hydrocarbons may be involved in urothelial carcinogenesis,6 A.H.H. might also affect the metabolism of arylamines.7 A consistent difference in A.H.H. inducibility pattern between smoke-related urothelial and respiratory-tract carcinomas would seem to be of considerable interest. We report here our results on A.H.H. inducibility assessments in carcinoma of the oral cavity. In the period 1966-76, 77 cases of squamous cell, oral, oropharyngeal, and epipharyngeal carcinomas were clinically diagnosed and histopathologically verified at the department of otorhinolaryngology, Malmö General Hospital. In the autumn of 1976, 50 were still alive, and all who were below eighty years of age (44) were invited to the section of preventive medicine, Malmö General Hospital, for A.H.H. assessment. 34 patients (13 gingival, 7 lingual, 5 epipharyngeal, 2 palatal, 5 other oral sites, 2 advanced leukoplakias), left venous blood-samples which were assessed for A.H.H. inducibility2 at the the department of tumour cytogenetics, Wallenberg Laboratory, Lund. tract cancers
ever, in 12
cases
A.H.H.
DISTRIBUTION*
AND NUMBER OF SMOKERS AND
NON-SMOKERS
*Expected numbers calculated from data of Kellerman et al.’ Male/female ratios shown in parentheses.
Hereditary, occupational, and smoking histories were obtained from all patients. The main results are summarised in the table. In the males (28 smokers, 1 non-smoker) but not in the females (3 smokers, 2 non-smokers), there was an over-representation of tobacco consumers. 3 of the men were asphalt workers. Occupational and family histories were otherwise unremarkable. There was a highly significant over-representation of high A.H.H. inducibility in the material. Although oral carcinomas form a heterogeneous group, we included only squamous-cell varieties, which have been shown to be clearly associated with smoking.8 The pattern in oral carcinoma seems similar to the over-representation of high A.H.H. inducibility found in smokedependent pulmonary’ and laryngeaP carcinomas, and supports the concept that A.H.H. plays an important role in the activation of carcinogens in various smoke-related airway tract cancers; this does not seem to apply in urothelial carcinogenesis. Section of Preventive Medicine and Departments of Internal Medicine and
Oto-Rhino-Laryngology, University of Lund, Hospital,
Malmö General
Malmö, Sweden; Research Department I and Department of Lung Medicine, University Hospital, Lund: and Department of Tumour Cytogenetics,
Wallenberg Laboratory, University of Lund
E. TRELL R. KORSGAARD P. KITZING K. LUNDGREN I. MATTIASSON
CROHN’S DISEASE RESPONDING TO ORAL DISODIUM CROMOGLYCATE
SIR,-A 25-year-old male presented in January, 1977, with 3-year history of weight loss, vague abdominal pain, and intermittent diarrhoea containing blood and mucus. Rectal a
biopsy and barium enema showd a mild non-specific proctitis. His haemoglobin was 10-0 g/dl, erythrocyte-sedimentation rate (E.S.R.) 51 mm/h, and serum-albumin 23 g/1. Ulcerative colitis was diagnosed and salazopyrine and steroid enemas were started. However, he did not respond satisfactorily and was admitted to hospital where he was transfused and given highdose oral steroids. His general health improved and the E.S.R. fell to 3 mm/h, but he did not gain weight, his diarrhoea persisted, and his serum-albumin remained low. A barium follow-
through disclosed extensive small-bowel Crohn’s disease. He was discharged on 30 mg prednisone daily, and during outpatient follow-up his weight slowly increased, his diarrhoea improved, and his serum-albumin rose to normal. His oral steroids were gradually reduced, but, though his haemoglobin and serum-albumin concentrations remained satisfactory, his E.S.R. 45 mm/h and he had severe clinical exacerbation unresoral metronidazole. He had to be admitted to hospital, where he was put on an elemental diet (’Vivonex’) and highdose oral steroids. Rectal biopsy confirmed Crohn’s disease. He did not improve and after a week a tender, indurated mass was noted in the right iliac fossa. Surgery was thought necessary, and while awaiting this, the patient was given oral disodium rose to
Kellerman, G., Shaw, C. R., Lyten-Kellerman, M. New Engl. J. Med. 1973, 289, 934. 2. Trell, E., Korsgaard, R., Hood, B., Kitzing, P., Nordén, G., Simonsson, B. G. Lancet, 1976, ii, 140. 3. Lilienfeld, A. M., Levin, M. L., Moore, G. E. Archs intern. Med. 1956, 98, 129. 4. Hammon, E. C., Horn, D.J. Am. med. Ass., 1958, 166, 294. 5. Trell, E., Oldbring, J., Korsgaard, R., Mattiasson, I. Lancet, 1977, ii, 612. 6. Kerr, W. K., Barkin, M., Levers, P. E., Woo, s.K-C., Menczyk, A. R. T. Can. med. Ass. J., 1965, 93, 1. 7 Miller, J. A., Miller, E. C. J. natn. Cancer Inst. 1971, 47, V.
ponsive
8.
Auerbach, O., 253.
Stout, A. P., Hammon, E. C. New Engl. J. Med. 1961, 265,
