Defects in bile pigment metabolism causing jaundice

The excretion of bilirubin and therefore the relief of jaundice is dependent upon at least three factors. First, the bilirubin must be conjugated and thus converted into a water soluble compound: this means its conversion to an ester glucuronide although other conjugates may also be formed. Secondly, there is the problem of the transport of bilirubin through the hepatic cell. A defect in either the up-take of bilirubin or the secretion of conjugated bilirubin may result in jaundice such as is seen in the various types of familial hyperbilirubinemia. Thirdly, there is the possibility of alternative catabolic pathways for bilirubin: this approach to the problem has, however, not yet received the attention of investigators.</p

Observations on the use of protein hydrolysates in medical and surgical cases

There can be little doubt that an enzymic hydrolysate of casein is an adequate source of protein food; the indications for its administration in preference to those of whole protein are, however, more difficult to find.The complexity of the changes in salt metabolism which result from operation is obvious. It is, there -fore, not surprising that no simple chemical estimation is of use in indicating the salt requirements of the patient at this time. The chloride concentration of the blood may give an erroneous impression, since salt retention has been observed with both raised and depressed values. Lack of salt in the urine is likewise no indication that the patient has not been given an adequate salt intake, since, for a variety of reasons, the patient is unable to excrete salt in the immediate post - operative period. A further knowledge of the problems involved is, therefore, required before a simple procedure can be found which will give the clinician a clear idea of his patients' salt requirements

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children