1250 head. The arthrosis can be explained as secondary to this fracture. This patient’s complaints and the X-ray abnormalities could have resulted from the electric shock. Arthrosis does not often occur spontaneously in a young man. Before his imprisonment he was healthy and had no
complaints.
Department of Internal Medicine III, University Hospital Dijkzigt, Rotterdam, Netherlands.
JEANNE SMEULERS.
analogues inhibited G.H. secretion in the normal and acromegalic subjects studied, but their duration of action in man appears to be no longer than that of the native compound. Insulin release was similarly suppressed by the G.H.-R.I.H. analogues. The two analogues studied appear to have no potential therapeutic advantage over G.H.-R.i.H. and had the disadvantage that they induced malaise and nausea after intravenous infusion in the 2 normal subjects. It is possible that the differences observed could be attributed to species specificity.
ANALOGUES OF GROWTH-HORMONE RELEASE-INHIBITING HORMONE
Endocrine Unit, Department of Medicine, University of Newcastle upon Tyne.
SIR,-Growth - hormone release - inhibiting hormone (G.H.-R.I.H.) is a potent inhibitor of growth hormone (G.H.) release in normal and acromegalic subjects 1,2 and also an inhibitor of insulin and glucagon release.a Early reports indicated that this peptide has a very short half-life,’,s thus reducing its therapeutic potential. A number of G.H.-R.I.H. analogues have been synthesised in an effort to obtain compounds with prolonged biological activity. Deletion of the N-terminal dipeptide (Ala-Gly2) is compatible with high biological activity in rats, and acylation of the third residue (Cys3) renders the molecule less soluble and prolongs its action. Brazeau et al.4 used an N-acetyl analogue in the reduced (linear) form and an N-benzoyl analogue in the oxidised (cyclised) form.
Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP. M.R.C. Growth and Reproduction
We should like to report the results of observations in normal subjects and one acromegalic patient who received infusions of these G.H.-R.I.H. analogues. The acylated des-(Alal-Gly2)-G.H.-R.i.H. analogues were used and both of these were prepared in the oxidised (native) form. One normal subject received N-acetyl-des-(AlalGly2)-G.H.-R.I.H. and the other N-benzoyl-des-(Ala1-Gly2)G.H.-R.I H. The experimental procedure was:
D. C. EVERED A. GOMEZ-PAN W. M. G. TUNBRIDGE. R. HALL.
Unit, Princess Mary Maternity Hospital, Newcastle upon Tyne.
T. LIND.
Medical Professorial Unit, St. Bartholomew’s Hospital, London.
G. M. BESSER C. H. MORTIMER M. O. THORNER.
Endocrine and
Polypeptide
Laboratories, Veterans Administration Hospital, Tulane University School of Medicine New Orleans, Louisiana, U.S.A.
A. V. SCHALLY A. J. KASTIN D. H. COY.
two
There was no rise in plasma-G.H. during the infusion of the G.H.-R.I.H. analogue in either subject in response to arginine infusion (maximum G.H. 1-9 ng. per ml. M.R.C. 69/46 standard in both subjects), but there was a rapid release of G.H. after the infusion was discontinued (G.H. levels 15 minutes after infusion 25-2 and 24-7 ng. per ml.). The rise in plasma-insulin in response to arginine was reduced during the infusion of the G.H.-R.I.H. analogues to 5-1 and 7-6 tu per ml. M.R.C. standard 66/304 compared with the earlier response to greater than 32 jjt.u per ml. in both subjects. The plasma-insulin level rose within 15 minutes of discontinuing the infusion to 11-9 and 12-8 ,v per ml. Each G.H.-R.l.H. analogue (500 g.) was given subcutaneously to an acromegalic subject who had previously been shown to have G.H. levels which were suppressed by G.H.-R.I.H. The G.H. levels were reduced to 50% of the basal level one hour after injection, but had returned to basal levels after a further hour. These observations are at variance with those reported in the rat.4 Both acylated des-(Ala I-Gly2)-G.H.-R.I.H. Hall, R., Besser, G. M., Schally, A. V., Coy, D. H., Evered, D. C., Goldie, D. J., Kastin, A. J., McNeilly, A. S., Mortimer, C. H., Phenekos, C., Tunbridge, W. M. G., Weightman, D. Lancet, 1973, ii, 581. 2. Besser, G. M., Mortimer, C. H., Carr, D., Schally, A. V., Coy, D. H., Evered, D., Kastin, A. J., Tunbridge, W. M. G., Thorner, M. O., Hall, R. Br. med. J. 1974, i, 352. 3. Mortimer, C. H., Tunbridge, W. M. G., Carr, D., Yeomans, L., Lind, T., Coy, D. H., Bloom, S. R., Kastin, A., Mallinson, C. N., Besser, G. M., Schally, A. V., Hall, R. Lancet, 1974, i, 697. 4. Brazeau, P., Vale, W., Rivier, J., Guillemin, R. Biochem. Biophys. Res. Comm. 1974, 60, 1202. 1.
INFANTILE CHRONIC RELAPSING INFLAMMATION OF THE BRAIN, SKIN, AND JOINTS
SIR,-Lorber1 described a boy who had had an undiagnosed complex syndrome involving a chronic neurological illness and a possible collagen disease since infancy. We found an almost identical case, a girl (case 1) who died aged 11 years with subacute necrotising leucoencephalopathy. We later saw a baby girl (case 2) who had recurrent erythematous lesions of the skin, recurrent painful swelling of joints, recurrent pleocytosis in the cerebrospinal fluid, and splenomegaly and iron-resistant hypochromic ansemia with neutrophilic leucocytosisall findings typical of this syndrome. Perhaps these cases represent a new clinical entity or an infantile variant of Behcet’s syndrome without oral or genital ulcers. Furthermore, in both our patients phytohsemagglutinin-induced lymphocyte blast cell transformation and the production of
lymphotoxin
were
impaired.
Case l.-Birth-weight 3020 g., gestational age 38 weeks. Since birth she had had an intermittent widespread rash, diagnosed as chronic urticaria by sweat test and biopsy. She had an ugly face with thin, scanty, blonde hair and protruding eyes. Her growth was below the 10th percentile at school age. Intellectual development was slow. Perceptive deafness was detected when she was 10 years old. Fontanelle open (1 x1 cm.) at 3 years. Bilateral pseudopapilloedema (2-4 dioptre) was found at 3 years and a visual defect at 10 years. Cells were repeatedly found in the cerebrospinal fluid (1-1450 per c.mm.). There was painful swelling of the right foot at 1 year, of the right knee, elbow, and of the wrists at 9 years, and of the left knee at 10 years. Her body temperature was constantly around 37-8°C. She had had recurrent splenomegaly since the age of 5, and lymphadenopathy since the age of 7. Heamoglobin was around 9-5 g. per 100 ml. Serum-iron was 10 g. per 100 ml., serum-copper 300 ng. per 100 ml., erythrocyte sedimentation rate (E.S.R.) around 45 per hour, IgG 2570 mg. per 100 ml. There was persistent leucocytosis around 13,000 per c.mm. Bone-marrow biopsy revealed hyperactive granulopoiesis (60%) (2-5% plasma-cells). 10 weeks before death right-sided hemiplegia developed after trauma and the patient became unconscious. A necrotic left temporal lobe was resected. Microscopically, brain biopsy showed subacute 1.
Lorber, J. Proc. R. Soc. Med. 1973, 66, 1070.
complaints.
Department of Internal Medicine III, University Hospital Dijkzigt, Rotterdam, Netherlands.
JEANNE SMEULERS.
analogues inhibited G.H. secretion in the normal and acromegalic subjects studied, but their duration of action in man appears to be no longer than that of the native compound. Insulin release was similarly suppressed by the G.H.-R.I.H. analogues. The two analogues studied appear to have no potential therapeutic advantage over G.H.-R.i.H. and had the disadvantage that they induced malaise and nausea after intravenous infusion in the 2 normal subjects. It is possible that the differences observed could be attributed to species specificity.
ANALOGUES OF GROWTH-HORMONE RELEASE-INHIBITING HORMONE
Endocrine Unit, Department of Medicine, University of Newcastle upon Tyne.
SIR,-Growth - hormone release - inhibiting hormone (G.H.-R.I.H.) is a potent inhibitor of growth hormone (G.H.) release in normal and acromegalic subjects 1,2 and also an inhibitor of insulin and glucagon release.a Early reports indicated that this peptide has a very short half-life,’,s thus reducing its therapeutic potential. A number of G.H.-R.I.H. analogues have been synthesised in an effort to obtain compounds with prolonged biological activity. Deletion of the N-terminal dipeptide (Ala-Gly2) is compatible with high biological activity in rats, and acylation of the third residue (Cys3) renders the molecule less soluble and prolongs its action. Brazeau et al.4 used an N-acetyl analogue in the reduced (linear) form and an N-benzoyl analogue in the oxidised (cyclised) form.
Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP. M.R.C. Growth and Reproduction
We should like to report the results of observations in normal subjects and one acromegalic patient who received infusions of these G.H.-R.I.H. analogues. The acylated des-(Alal-Gly2)-G.H.-R.i.H. analogues were used and both of these were prepared in the oxidised (native) form. One normal subject received N-acetyl-des-(AlalGly2)-G.H.-R.I.H. and the other N-benzoyl-des-(Ala1-Gly2)G.H.-R.I H. The experimental procedure was:
D. C. EVERED A. GOMEZ-PAN W. M. G. TUNBRIDGE. R. HALL.
Unit, Princess Mary Maternity Hospital, Newcastle upon Tyne.
T. LIND.
Medical Professorial Unit, St. Bartholomew’s Hospital, London.
G. M. BESSER C. H. MORTIMER M. O. THORNER.
Endocrine and
Polypeptide
Laboratories, Veterans Administration Hospital, Tulane University School of Medicine New Orleans, Louisiana, U.S.A.
A. V. SCHALLY A. J. KASTIN D. H. COY.
two
There was no rise in plasma-G.H. during the infusion of the G.H.-R.I.H. analogue in either subject in response to arginine infusion (maximum G.H. 1-9 ng. per ml. M.R.C. 69/46 standard in both subjects), but there was a rapid release of G.H. after the infusion was discontinued (G.H. levels 15 minutes after infusion 25-2 and 24-7 ng. per ml.). The rise in plasma-insulin in response to arginine was reduced during the infusion of the G.H.-R.I.H. analogues to 5-1 and 7-6 tu per ml. M.R.C. standard 66/304 compared with the earlier response to greater than 32 jjt.u per ml. in both subjects. The plasma-insulin level rose within 15 minutes of discontinuing the infusion to 11-9 and 12-8 ,v per ml. Each G.H.-R.l.H. analogue (500 g.) was given subcutaneously to an acromegalic subject who had previously been shown to have G.H. levels which were suppressed by G.H.-R.I.H. The G.H. levels were reduced to 50% of the basal level one hour after injection, but had returned to basal levels after a further hour. These observations are at variance with those reported in the rat.4 Both acylated des-(Ala I-Gly2)-G.H.-R.I.H. Hall, R., Besser, G. M., Schally, A. V., Coy, D. H., Evered, D. C., Goldie, D. J., Kastin, A. J., McNeilly, A. S., Mortimer, C. H., Phenekos, C., Tunbridge, W. M. G., Weightman, D. Lancet, 1973, ii, 581. 2. Besser, G. M., Mortimer, C. H., Carr, D., Schally, A. V., Coy, D. H., Evered, D., Kastin, A. J., Tunbridge, W. M. G., Thorner, M. O., Hall, R. Br. med. J. 1974, i, 352. 3. Mortimer, C. H., Tunbridge, W. M. G., Carr, D., Yeomans, L., Lind, T., Coy, D. H., Bloom, S. R., Kastin, A., Mallinson, C. N., Besser, G. M., Schally, A. V., Hall, R. Lancet, 1974, i, 697. 4. Brazeau, P., Vale, W., Rivier, J., Guillemin, R. Biochem. Biophys. Res. Comm. 1974, 60, 1202. 1.
INFANTILE CHRONIC RELAPSING INFLAMMATION OF THE BRAIN, SKIN, AND JOINTS
SIR,-Lorber1 described a boy who had had an undiagnosed complex syndrome involving a chronic neurological illness and a possible collagen disease since infancy. We found an almost identical case, a girl (case 1) who died aged 11 years with subacute necrotising leucoencephalopathy. We later saw a baby girl (case 2) who had recurrent erythematous lesions of the skin, recurrent painful swelling of joints, recurrent pleocytosis in the cerebrospinal fluid, and splenomegaly and iron-resistant hypochromic ansemia with neutrophilic leucocytosisall findings typical of this syndrome. Perhaps these cases represent a new clinical entity or an infantile variant of Behcet’s syndrome without oral or genital ulcers. Furthermore, in both our patients phytohsemagglutinin-induced lymphocyte blast cell transformation and the production of
lymphotoxin
were
impaired.
Case l.-Birth-weight 3020 g., gestational age 38 weeks. Since birth she had had an intermittent widespread rash, diagnosed as chronic urticaria by sweat test and biopsy. She had an ugly face with thin, scanty, blonde hair and protruding eyes. Her growth was below the 10th percentile at school age. Intellectual development was slow. Perceptive deafness was detected when she was 10 years old. Fontanelle open (1 x1 cm.) at 3 years. Bilateral pseudopapilloedema (2-4 dioptre) was found at 3 years and a visual defect at 10 years. Cells were repeatedly found in the cerebrospinal fluid (1-1450 per c.mm.). There was painful swelling of the right foot at 1 year, of the right knee, elbow, and of the wrists at 9 years, and of the left knee at 10 years. Her body temperature was constantly around 37-8°C. She had had recurrent splenomegaly since the age of 5, and lymphadenopathy since the age of 7. Heamoglobin was around 9-5 g. per 100 ml. Serum-iron was 10 g. per 100 ml., serum-copper 300 ng. per 100 ml., erythrocyte sedimentation rate (E.S.R.) around 45 per hour, IgG 2570 mg. per 100 ml. There was persistent leucocytosis around 13,000 per c.mm. Bone-marrow biopsy revealed hyperactive granulopoiesis (60%) (2-5% plasma-cells). 10 weeks before death right-sided hemiplegia developed after trauma and the patient became unconscious. A necrotic left temporal lobe was resected. Microscopically, brain biopsy showed subacute 1.
Lorber, J. Proc. R. Soc. Med. 1973, 66, 1070.
