- Email: [email protected]
NERVOUS SYSTEM IN PORPHYRIA
851 Cortisone in the relatively high doses used by Dr. Barta and Dr. Simon is likely to depress the activity of the anterior lobe of the pituitary and of the adrenal cortex and so make their rabbits more sensitive to insulin. This would explain the increased blood-sugar falls due to insulin in their cortisone-treated rabbits. It is difficult, however, to understand why hypoglycæmic shock did not occur with insulin in their cortisone-treated rabbits, during cortisone treatment, if the bloodsugar fell to shock-producing levels. Cortisone appears to have some form of stimulating effect on the cerebral cortex at normal or raised blood-sugar levels, but there is no clear evidence that it has this effect or will mitigate the effects of hypoglycaemia at coma-producing bloodsugar
to the formation of this substance in the liver would lead to an excessive production and urinary excretion of porphobilinogen b and to demyelination of the nervous system. A genetically determined deficiency in a specific enzyme, variable in the expression of its severity, might explain the " block." The intermittent nature of the disease would then be related to the effect of other factors - e.g., endocrine changes, infection, and barbiturateson this abnormally sensitive pathway. The neuropsychiatric features of acute porphyria, as well as its pathological chemistry, can be explained on
this
hypothesis.
Department
of
Medicine,
Gardiner Institute, Western Infirmary, Glasgow, W.1.
levels.
A. GOLDBERG.
The Mental Hospitals’
Group Laboratory,
Obituary
West Park Hospital,
W. W. KAY. Epsom, Surrey. APOPLEXY OF YOUTH recent SIR,—A experience in the postmortem room add me to another cause of apoplexy in young prompts adults to those mentioned in your leading article of Oct. 5. The subject of the necropsy was a 16-year-old schoolboy who admitted to hospital in deep coma after he had collapsed suddenly at his home while going to bed. A few days previously he had complained of headache but otherwise he had been well and had taken full part in school activities. Clinical findings included a blood-pressure of 160/90 and heavily blood-stained cerebrospinal fluid. He died shortly after admission. At necropsy a large fresh haemorrhage was found in the substance of the left cerebrum, mainly in the region of the internal capsule. The heart weighed 450 g. and the enlargement was due to hypertrophy of the left ventricle, the wall of which was up to 2-5 cm. thick. The medulla of the right adrenal gland was replaced by a rounded phaeochromocytoma 3 cm. in diameter. was
The cause of apoplexy in this youth was clearly hyperpiesis due to an occult physiologically active phaeochromocytoma. Kent and Canterbury Hospital,
Canterbury.
G. B. FORBES.
NERVOUS SYSTEM IN PORPHYRIA SiR, Your annotation (Sept. 14) fails to mention relevant experimental work which renders unlikely the suggestion that a neurotoxic agent is responsible for the nervous and mental symptoms in porphyria. It has been
shown that purified porphyrins, acute-porphyria urine, and porphobilinogen are pharmacologically inactive ; there is moreover no evidence that a circulating vasoconstrictor substance exists in this disease.’ This view is strengthened by the production of an experimental porphyria in rabbits, rats, and fowls by the non-hypnotic substance allyl-isopropyl acetamide.2 The animals excreted large amounts of porphyrins and porphobilinogen, but showed no clinical features in common with human acute porphyria, apart from constipation and loss of weight. In acute porphyria there is a fundamental disturbance of pyrrole pigment metabolism which has its site in the livery Associated with this there may be a related dis= turbance in the metabolism of the nervous system, of
which
demyelination
is the
pathological expression.
The
exact nature of this association is not clear. The porphyrin-like structure of vitamin B124 demonstrates that at least one tetra-pyrrolic substance is essential for myelination of the nervous system. Some other tetrapyrrole, formed in the liver and of which porphobilinogen is a precursor, may also be essential for the nutrition of the myelin of the nervous system. A metabolic block " 1. Goldberg, A., Paton, W. D. M., Thompson, J. W. Brit. J. Pharmacol. 1954, 9, 91. 2. Goldberg, A., Rimington, C. Proc. Roy. Soc. B. (1955) 143, 257. 3. Goldberg, A. Lancet, 1954, ii, 172. 4. Bonner, R., Cannon, J. R., Johnson, A. W., Sutherland, I., Todd, A. R. Nature Lond. 1955, 176, 328. "
ARTHUR JOHN CLEVELAND O.B.E., M.D. Lond., F.R.C.P. Dr. A. J. Cleveland, consulting physician to the Norfolk and Norwich Hospital, died on Oct. 8 at the age of 85. He was born in Brighton, the son of a solicitor to the Government in Bombay. From Clifton College he went to Guy’s Hospital, where, after qualifying in 1897, he held posts as house-physician, medical registrar, and medical tutor. During the five years he held these posts he took the M.D. and the M.R.c.P. In 1902 he settled in Norwich in general practice, and two years later he was appointed to the Norfolk and Norwich Hospital as its first radiologist. In 1905 he was elected assistant physician to the hospital. During the 1914-18 war he was attached as physician, with the rank of major, to the
Thorpe Military Hospital, and he was appointed O.B.E.
for his services. Cleveland’s chief interest was neurology, and until a year or so before his death he acted as consultant in neurology to the Ministry of Pensions ; a lesser interest was dermatology. But it is as
an
outstanding hospital
administrator that he will be remembered. He was chairman of the board of governors of the Norfolk and Norwich Hospital during the critical years from 1938 to 1943. He played an important part in creating special departments and, with the late Frank Inch, secretary and house-governor, in founding a private patients’ department. He was active in satting up a scheme of insurance whereby people of moderate means could obtain specialised treatment in a nursinghome. His history of the hospital from 1900 to the end of 1946 brought the earlier history by Sir Peter Eade up to date. Largely as a result of the impression he had made in
hospital management, Cleveland, though taking no part in local politics, was, in 1943 at the age of 70, elected
Lord Mayor of Norwich-an office which he filled with energy and dignity. For ten years he was a director of As an afterthe Norwich Union Insurance Societies. dinner speaker he was outstanding, and his name on a toast list never failed to attract a large audience to any medical gathering. B.B.M. writes: Gifted with a logical, analytical, and, above all, a far-seeing
brain, Cleveland
was
at his best
on
committee and
was an
outstanding chairman. He held strong views on the importance of medical staff influencing the policy of the hospital. He was forthright in putting forward the views of the staff and adamant in opposing exploitation of their services or invasion of their rights. To him in large measure was due the cordial and 5.
Goldberg, A. Lancet, 1954, ii, 1095.
to the formation of this substance in the liver would lead to an excessive production and urinary excretion of porphobilinogen b and to demyelination of the nervous system. A genetically determined deficiency in a specific enzyme, variable in the expression of its severity, might explain the " block." The intermittent nature of the disease would then be related to the effect of other factors - e.g., endocrine changes, infection, and barbiturateson this abnormally sensitive pathway. The neuropsychiatric features of acute porphyria, as well as its pathological chemistry, can be explained on
this
hypothesis.
Department
of
Medicine,
Gardiner Institute, Western Infirmary, Glasgow, W.1.
levels.
A. GOLDBERG.
The Mental Hospitals’
Group Laboratory,
Obituary
West Park Hospital,
W. W. KAY. Epsom, Surrey. APOPLEXY OF YOUTH recent SIR,—A experience in the postmortem room add me to another cause of apoplexy in young prompts adults to those mentioned in your leading article of Oct. 5. The subject of the necropsy was a 16-year-old schoolboy who admitted to hospital in deep coma after he had collapsed suddenly at his home while going to bed. A few days previously he had complained of headache but otherwise he had been well and had taken full part in school activities. Clinical findings included a blood-pressure of 160/90 and heavily blood-stained cerebrospinal fluid. He died shortly after admission. At necropsy a large fresh haemorrhage was found in the substance of the left cerebrum, mainly in the region of the internal capsule. The heart weighed 450 g. and the enlargement was due to hypertrophy of the left ventricle, the wall of which was up to 2-5 cm. thick. The medulla of the right adrenal gland was replaced by a rounded phaeochromocytoma 3 cm. in diameter. was
The cause of apoplexy in this youth was clearly hyperpiesis due to an occult physiologically active phaeochromocytoma. Kent and Canterbury Hospital,
Canterbury.
G. B. FORBES.
NERVOUS SYSTEM IN PORPHYRIA SiR, Your annotation (Sept. 14) fails to mention relevant experimental work which renders unlikely the suggestion that a neurotoxic agent is responsible for the nervous and mental symptoms in porphyria. It has been
shown that purified porphyrins, acute-porphyria urine, and porphobilinogen are pharmacologically inactive ; there is moreover no evidence that a circulating vasoconstrictor substance exists in this disease.’ This view is strengthened by the production of an experimental porphyria in rabbits, rats, and fowls by the non-hypnotic substance allyl-isopropyl acetamide.2 The animals excreted large amounts of porphyrins and porphobilinogen, but showed no clinical features in common with human acute porphyria, apart from constipation and loss of weight. In acute porphyria there is a fundamental disturbance of pyrrole pigment metabolism which has its site in the livery Associated with this there may be a related dis= turbance in the metabolism of the nervous system, of
which
demyelination
is the
pathological expression.
The
exact nature of this association is not clear. The porphyrin-like structure of vitamin B124 demonstrates that at least one tetra-pyrrolic substance is essential for myelination of the nervous system. Some other tetrapyrrole, formed in the liver and of which porphobilinogen is a precursor, may also be essential for the nutrition of the myelin of the nervous system. A metabolic block " 1. Goldberg, A., Paton, W. D. M., Thompson, J. W. Brit. J. Pharmacol. 1954, 9, 91. 2. Goldberg, A., Rimington, C. Proc. Roy. Soc. B. (1955) 143, 257. 3. Goldberg, A. Lancet, 1954, ii, 172. 4. Bonner, R., Cannon, J. R., Johnson, A. W., Sutherland, I., Todd, A. R. Nature Lond. 1955, 176, 328. "
ARTHUR JOHN CLEVELAND O.B.E., M.D. Lond., F.R.C.P. Dr. A. J. Cleveland, consulting physician to the Norfolk and Norwich Hospital, died on Oct. 8 at the age of 85. He was born in Brighton, the son of a solicitor to the Government in Bombay. From Clifton College he went to Guy’s Hospital, where, after qualifying in 1897, he held posts as house-physician, medical registrar, and medical tutor. During the five years he held these posts he took the M.D. and the M.R.c.P. In 1902 he settled in Norwich in general practice, and two years later he was appointed to the Norfolk and Norwich Hospital as its first radiologist. In 1905 he was elected assistant physician to the hospital. During the 1914-18 war he was attached as physician, with the rank of major, to the
Thorpe Military Hospital, and he was appointed O.B.E.
for his services. Cleveland’s chief interest was neurology, and until a year or so before his death he acted as consultant in neurology to the Ministry of Pensions ; a lesser interest was dermatology. But it is as
an
outstanding hospital
administrator that he will be remembered. He was chairman of the board of governors of the Norfolk and Norwich Hospital during the critical years from 1938 to 1943. He played an important part in creating special departments and, with the late Frank Inch, secretary and house-governor, in founding a private patients’ department. He was active in satting up a scheme of insurance whereby people of moderate means could obtain specialised treatment in a nursinghome. His history of the hospital from 1900 to the end of 1946 brought the earlier history by Sir Peter Eade up to date. Largely as a result of the impression he had made in
hospital management, Cleveland, though taking no part in local politics, was, in 1943 at the age of 70, elected
Lord Mayor of Norwich-an office which he filled with energy and dignity. For ten years he was a director of As an afterthe Norwich Union Insurance Societies. dinner speaker he was outstanding, and his name on a toast list never failed to attract a large audience to any medical gathering. B.B.M. writes: Gifted with a logical, analytical, and, above all, a far-seeing
brain, Cleveland
was
at his best
on
committee and
was an
outstanding chairman. He held strong views on the importance of medical staff influencing the policy of the hospital. He was forthright in putting forward the views of the staff and adamant in opposing exploitation of their services or invasion of their rights. To him in large measure was due the cordial and 5.
Goldberg, A. Lancet, 1954, ii, 1095.