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CONGENITAL NON-HÆMOLYTIC JAUNDICE
322
therefore it seems unreasonable to be fussy about visits in this country to towns in which so few cases have occurred while at the same time taking no steps to restrict arrival from areas of high prevalence. I have several times in the last few days been disagreeably impressed by those who have produced international certificates, elaborately stamped, and have given contrary stories about the date of their vaccination and have produced to my sceptical gaze ancient scars which they claimed had been given within the last week or two. It would be rash in the extreme to invite neighbours over from the next district if smallpox were prevalent there: why, in the name of logic, is it not clearly unreasonable to allow free access from another country? Would some expert clear my mind ? R. C. WEBSTER. Accrington, Lancs. POST-VACCINAL ENCEPHALITIS SIR,-Among the millions of people now being vaccinated a few cases of post-vaccinal encephalitis may be encountered. May I suggest that transfusion of immune blood be considered in such cases ? I have seen only one case,l but other reports of favourable results have appeared from time to time. My patient, a young soldier, showed a quite dramatic improvement within twenty-four hours after a transfusion of a pint of blood from a recently vaccinated donor. Royal Victoria Hospital, Boscombe, Bournemouth, Hants.
R. V. FACEY.
SMALLPOX VACCINATION AND HERPES SIR,-" These herpetic affections which so frequently appear among the children of the poor, and which are evidently contagious, often prevent the vaccine virus from producing its correct action." So said Dr. Jenner in a paper to the Medical and Physical Journal in 1805. This observation is singularly relevant at present and I wonder to what extent it still applies. As Dr. Alick Isaacs has said, this may have been one of the earliest records of viral interference and could well have been due to interferon since the herpes-simplex virus is known to stimulate its production. Conversely, Dr. Jenner also observed that vaccination sometimes improves longstanding herpes: I do not mean to say, that the pustule is always imperfect, and not effective, when the "
inoculated patient has this malady; on the contrary, it is some-, times perfectly correct, and much more frequently so when it has been of long standing, than when in its recent state, and what is remarkable, the disease is then (when of long duration) sometimes swept entirely away." Now that larger numbers of people are presenting themselves for vaccination, there is an opportunity to satisfy ourselves on these two points. Ruislip, ANDREWS. NDREWS.
R. D R D. Middlesex...
CIVILISATION AND PEPTIC ULCER SIR,-The excellent paper of Jan. 20 by Dr. Susser and Dr. Stein offers considerable evidence against mental stress being the direct cause of these diseases. Indeed, even these careful workers cannot quite lay the ghost. After arguing that stresses are likely " to increase or at least continue as our society grows more complex ..." " they write: However, it could be a disease of an early phase of urbanisation ". It could, but direct bacteriological or chemical attack would appear to be more likely factors. 1.
Facey, R. V. Lancet, 1942, ii, 669.
The decline in the number and
severity
of
gastrointestinal
disorders, and weaker alcoholic drinks, may have blunted this attack; but the strongest assault probably came with the introduction of acetylsaliscyclic acid in 1899. It is true that the cohort analysis shows peaks in the younger groups before the introduction of aspirin, but a detailed study of the death-rates showed, for gastric and duodenal ulcers in males, that the generations born in 1885 and 1890 respectively carried the highest risk of dying from peptic ulceration, and the death-rate below 15 years of age was, even in 1900, very low. The stresses and strains of war were also likely to alter dietary habits in the consumption of alcohol and aspirin and possibly other drugs. These are particularly likely to be taken by older persons who, in their youth, had very little else to tranquillise them. It is tempting to relate duodenal ulcer (and lung and stomach carcinoma) in males to the change from pipe and cigar to cigar. ette smoking with the change of site of the products of combustion from the stomach to the lung but at least it can be said with some certainty that gastric ulcer in females is not caused by
cigarette smoking.
J. P. W. HUGHES.
London, W.8.
CONGENITAL NON-HÆMOLYTIC JAUNDICE SIR,-A rare form of congenital disturbance of bilirubin metabolism is named after Crigler and Najjar,l who first described it. The most striking feature is a non-obstructive non-haemolytic jaundice. This is usually attributed to a defect in the liver enzyme, glucuronosyl transferase, which converts bilirubin to its glucuronide, and which is normally excreted in the bile. In-vivo studieshave shown that, after the administration of aglycones other than bilirubin, the formation of glucuronides is much reduced. We now report the in-vitro determination of glucuronosyl transferase in a sample of liver from one of two siblings affected with the Crigler-Najjar syndrome: The two patients, a brother and a sister, have a constant jaundice due to unconjugated bilirubin at a plasma concentration of 16-5 to 48 mg. per 100 ml. They were the first and second pregnancies of apparently normal parents. They both had kernicterus during the first month of life, and in-vivo administration of menthol and N-acetyl-para-aminophenol showed reduced excretion the corresponding glucuronides. At the age of 6 months a laparotomy was performed on the boy and 0-5 g. of liver was obtained. It was immediately homogenised and added to a solution of 20% bilirubin in bovine albumin. A boiled extract of liver was added to provide uridine diphosphate glucuronic acid. Samples of the mixture were taken, before and after 45 minutes’ incubation, for determination of direct-reacting bilirubin, according to the technique of Grodsky and Carbone.3 Incubation did not increase the amount of direct-reacting (i.e., conjugated) bilirubin. A control sample of rat liver, treated in the same way, gave a 3’5-fold increase in the direct-reacting bilirubin. We conclude that the liver glucuronosyl transferase is either absent, or inactive, possibly owing to the inhibitor described by Lathe and Walker.4 However, no inhibitor could be found in a sample of serum examined by J. B. Holton, of the department of chemical pathology, University of Leeds. Our direct enzyme studies thus confirm that the Crigler-Najjar syndrome is due to a congenital absence of glucuronosyl transferase of liver. The cases will be I-Iungarica.
published
in detail in the Acta Pcediatrica
Department of Pædiatrics, Medical University, Szeged, Hungary. 1. 2. 3. 4.
L. SZABÓ Z. KOVÁCS P. ÉBREY.
Crigler, J. F., Najjar, V. A. Pediatrics, 1952, 10, 169. Schmid, R. J. clin. Invest. 1957, 35, 927. Grodsky, G. M., Carbone, J. V. J. biol. Chem. 1957, 226, 449. Lathe, G. H., Walker, M. Quart. J. exp. Physiol. 1958, 43, 257.
therefore it seems unreasonable to be fussy about visits in this country to towns in which so few cases have occurred while at the same time taking no steps to restrict arrival from areas of high prevalence. I have several times in the last few days been disagreeably impressed by those who have produced international certificates, elaborately stamped, and have given contrary stories about the date of their vaccination and have produced to my sceptical gaze ancient scars which they claimed had been given within the last week or two. It would be rash in the extreme to invite neighbours over from the next district if smallpox were prevalent there: why, in the name of logic, is it not clearly unreasonable to allow free access from another country? Would some expert clear my mind ? R. C. WEBSTER. Accrington, Lancs. POST-VACCINAL ENCEPHALITIS SIR,-Among the millions of people now being vaccinated a few cases of post-vaccinal encephalitis may be encountered. May I suggest that transfusion of immune blood be considered in such cases ? I have seen only one case,l but other reports of favourable results have appeared from time to time. My patient, a young soldier, showed a quite dramatic improvement within twenty-four hours after a transfusion of a pint of blood from a recently vaccinated donor. Royal Victoria Hospital, Boscombe, Bournemouth, Hants.
R. V. FACEY.
SMALLPOX VACCINATION AND HERPES SIR,-" These herpetic affections which so frequently appear among the children of the poor, and which are evidently contagious, often prevent the vaccine virus from producing its correct action." So said Dr. Jenner in a paper to the Medical and Physical Journal in 1805. This observation is singularly relevant at present and I wonder to what extent it still applies. As Dr. Alick Isaacs has said, this may have been one of the earliest records of viral interference and could well have been due to interferon since the herpes-simplex virus is known to stimulate its production. Conversely, Dr. Jenner also observed that vaccination sometimes improves longstanding herpes: I do not mean to say, that the pustule is always imperfect, and not effective, when the "
inoculated patient has this malady; on the contrary, it is some-, times perfectly correct, and much more frequently so when it has been of long standing, than when in its recent state, and what is remarkable, the disease is then (when of long duration) sometimes swept entirely away." Now that larger numbers of people are presenting themselves for vaccination, there is an opportunity to satisfy ourselves on these two points. Ruislip, ANDREWS. NDREWS.
R. D R D. Middlesex...
CIVILISATION AND PEPTIC ULCER SIR,-The excellent paper of Jan. 20 by Dr. Susser and Dr. Stein offers considerable evidence against mental stress being the direct cause of these diseases. Indeed, even these careful workers cannot quite lay the ghost. After arguing that stresses are likely " to increase or at least continue as our society grows more complex ..." " they write: However, it could be a disease of an early phase of urbanisation ". It could, but direct bacteriological or chemical attack would appear to be more likely factors. 1.
Facey, R. V. Lancet, 1942, ii, 669.
The decline in the number and
severity
of
gastrointestinal
disorders, and weaker alcoholic drinks, may have blunted this attack; but the strongest assault probably came with the introduction of acetylsaliscyclic acid in 1899. It is true that the cohort analysis shows peaks in the younger groups before the introduction of aspirin, but a detailed study of the death-rates showed, for gastric and duodenal ulcers in males, that the generations born in 1885 and 1890 respectively carried the highest risk of dying from peptic ulceration, and the death-rate below 15 years of age was, even in 1900, very low. The stresses and strains of war were also likely to alter dietary habits in the consumption of alcohol and aspirin and possibly other drugs. These are particularly likely to be taken by older persons who, in their youth, had very little else to tranquillise them. It is tempting to relate duodenal ulcer (and lung and stomach carcinoma) in males to the change from pipe and cigar to cigar. ette smoking with the change of site of the products of combustion from the stomach to the lung but at least it can be said with some certainty that gastric ulcer in females is not caused by
cigarette smoking.
J. P. W. HUGHES.
London, W.8.
CONGENITAL NON-HÆMOLYTIC JAUNDICE SIR,-A rare form of congenital disturbance of bilirubin metabolism is named after Crigler and Najjar,l who first described it. The most striking feature is a non-obstructive non-haemolytic jaundice. This is usually attributed to a defect in the liver enzyme, glucuronosyl transferase, which converts bilirubin to its glucuronide, and which is normally excreted in the bile. In-vivo studieshave shown that, after the administration of aglycones other than bilirubin, the formation of glucuronides is much reduced. We now report the in-vitro determination of glucuronosyl transferase in a sample of liver from one of two siblings affected with the Crigler-Najjar syndrome: The two patients, a brother and a sister, have a constant jaundice due to unconjugated bilirubin at a plasma concentration of 16-5 to 48 mg. per 100 ml. They were the first and second pregnancies of apparently normal parents. They both had kernicterus during the first month of life, and in-vivo administration of menthol and N-acetyl-para-aminophenol showed reduced excretion the corresponding glucuronides. At the age of 6 months a laparotomy was performed on the boy and 0-5 g. of liver was obtained. It was immediately homogenised and added to a solution of 20% bilirubin in bovine albumin. A boiled extract of liver was added to provide uridine diphosphate glucuronic acid. Samples of the mixture were taken, before and after 45 minutes’ incubation, for determination of direct-reacting bilirubin, according to the technique of Grodsky and Carbone.3 Incubation did not increase the amount of direct-reacting (i.e., conjugated) bilirubin. A control sample of rat liver, treated in the same way, gave a 3’5-fold increase in the direct-reacting bilirubin. We conclude that the liver glucuronosyl transferase is either absent, or inactive, possibly owing to the inhibitor described by Lathe and Walker.4 However, no inhibitor could be found in a sample of serum examined by J. B. Holton, of the department of chemical pathology, University of Leeds. Our direct enzyme studies thus confirm that the Crigler-Najjar syndrome is due to a congenital absence of glucuronosyl transferase of liver. The cases will be I-Iungarica.
published
in detail in the Acta Pcediatrica
Department of Pædiatrics, Medical University, Szeged, Hungary. 1. 2. 3. 4.
L. SZABÓ Z. KOVÁCS P. ÉBREY.
Crigler, J. F., Najjar, V. A. Pediatrics, 1952, 10, 169. Schmid, R. J. clin. Invest. 1957, 35, 927. Grodsky, G. M., Carbone, J. V. J. biol. Chem. 1957, 226, 449. Lathe, G. H., Walker, M. Quart. J. exp. Physiol. 1958, 43, 257.