The validation and use of specific methods for the estimation of lipoprotein lipase and hepatic lipase activities in post-heparin plasma of children with hyperlipidaemia.

The methods proposed by Nilsson-Ehle and Ekman [8] for the specific estimation of lipoprotein lipase and hepatic lipase activities in post-heparin plasma were investigated. The procedure for hepatic lipase was found to be specific, but the lipoprotein lipase assay required modification to abolish hepatic lipase interference. The modified procedures were fully validated and found to be relatively simple, rapid and specific and were used to investigate children with primary and secondary hyperlipidaemic states.

The validation of a fluoroimmunoassay for the determination of theophylline concentration in dried blood spots suitable for domiciliary therapeutic drug monitoring.

A commercially available substrate-labelled fluorescent immunoassay procedure has been modified to create a simple rapid method for the determination of capillary theophylline concentration in the dried filter paper blood spots of patients on theophylline therapy. The specimens are collected and dispatched to the laboratory by the patient; thus domiciliary monitoring of theophylline therapy can take place. The technique offers a convenient method for overcoming many of the practical problems that arise during theophylline therapy in asthmatic patients.

A phenytoin assay using dried blood spot samples suitable for domiciliary therapeutic drug monitoring.

A commercially available substrate-labelled fluorescent immunoassay procedure has been modified to create a simple rapid method for the determination of capillary phenytoin concentration in dried filter paper blood spots of patients on phenytoin therapy. The specimens are collected and dispatched to the laboratory by the patient, thus domiciliary monitoring of phenytoin therapy can take place. The technique was validated by comparing the phenytoin results of simultaneously collected capillary dried blood spots and conventional plasma samples. The technique offers a convenient method for overcoming many of the practical problems of monitoring phenytoin therapy in epilepsy.

The activity of hepatic lipase and lipoprotein lipase in glycogen storage disease: evidence for a circulating inhibitor of postheparin lipolytic activity.

This study was designed to investigate the greatly reduced activities of hepatic lipase and lipoprotein lipase in postheparin plasma of patients with glycogen storage disease (GSD). Evidence for the presence of a circulating inhibitor in the plasma of GSD patients prior to the establishment of metabolic control was provided by the following observations. The hepatic lipase activity from patients with GSD gave a nonlinear relationship with time, maximum activity being obtained after 5 min whereas normal postheparin plasma showed a linear relationship for at least 20 min. The addition of GSD plasma to a normal postheparin plasma resulted in inhibition of the normal postheparin lipolytic activity. The inhibition showed a dose response, with 10 and 30 microliter of the GSD plasma giving 22 and 65% inhibition after 20 min, respectively. Serial dilution of GSD postheparin plasma gave increasing activity of hepatic lipase when expressed per ml of plasma. Thus, a 1:100 dilution gave a normal activity of 15 mumol/ml/h whereas a 1:10 dilution gave less than 10% of this activity. After affinity chromatography of the GSD postheparin plasma on heparin/Sepharose, the inhibition was removed and a normal lipolytic activity was obtained.

Cerebellar haemangioblastoma and genitourinary tumours.

In a series of 24 patients with cerebellar haemangioblastoma two subsequently developed renal carcinoma and one was found to have an epididymal tumour. The association between renal carcinoma and cerebellar haemangioblastoma is discussed. Repeated investigation of the genitourinary tract is advised in all cases of cerebellar haemangioblastoma to detect renal carcinoma before metastases have developed.

Vitamin D intoxication treated with porcine calcitonin.

Porcine calcitonin was used to treat three patients with hypercalcaemia due to vitamin D intoxication. In two patients a rapid and sustained fall to normal in serum calcium occurred within three days, in the third patient normocalcaemia was achieved in seven days. In view of its rapid and sustained effect calcitonin may be of value in the urgent treatment of hypercalcaemia due to vitamin D intoxication.

Relationship between plasma high-density lipoprotein concentrations and lipoprotein lipase and hepatic lipase activities in children with hyperlipidaemia.

1. Significant positive correlations were found between the lipoprotein lipase and hepatic lipase activities of post-heparin plasma samples and plasma high-density-lipoprotein (HDL) cholesterol concentrations in 21 children with hyperlipidaemia and six normal adult males. 2. A significant positive correlation was also observed between the two lipase activities and the ratio of HDL cholesterol to apoprotein AI (apo AI) concentrations. 3. These findings provide further evidence that a significant proportion of HDL and possibly the HDL, subfraction is formed during the clearance of triglyceride-rich lipoproteins.

Measles antibodies and autoantibodies in autoimmune disorders.

Measles CF antibodies have been examined in the sera of patients with a variety of clinical disorders associated with the production of autoantibodies. Previous reports of high-titre reactions in DLE and chronic active hepatitis have been confirmed, the titres in the latter disorder being particularly elevated. Mean antibody titres to measles in patients with rheumatoid arthritis were significantly lower than in matched controls, and an inverse correlation between measles antibody levels and serum globulin levels was found. Measles antibody titres in patients with myasthenia gravis and primary biliary cirrhosis did not differ significantly from those found in controls. However, subdivision of patients with rheumatoid arthritis, myasthenia gravis and primary biliary cirrhosis showed that the presence of anti-nuclear antibody (ANA) was associated with significantly increased measles antibody levels compared with the ANA-negative sera. The presence of gastric parietal cell antibody or thyroid microsomal antibody did not appear to be associated with increased measles antibody levels, whether or not they occurred in association with previous anaemia or thyroid disease. Possible explanations for these findings in terms of immune complex formation and immune hyper-reactivity are discussed.

Liver abnormalities and gallstones: a prospective combined clinical, histological and surgical study.

In a prospective study of 57 patients coming to elective cholecystectomy for gallstone disease, clinical, biochemical and immunological features have been correlated with the histological changes in core biopsies of the liver obtained at surgery. Only 13 liver biopsies were normal. Ten biopsies showed changes of acute duct obstruction, 16 showed minimal portal tract abnormalities and 10 showed moderate portal tract inflammation and scarring. Histological changes were more marked in male patients. Clinical and biochemical investigations were not useful in predicting histological appearance, apart from cases with jaundice at the time of operation where changes of acute duct obstruction were usually, but not invariably, seen. Atuo-antibodies were present in 50 per cent of cases tested and all persisted for at least 6 months after operation. They were commoner in patients with more marked histological changes. Operative cholangiography was of little use in predicting histological change. These findings suggest that the possibility of gallstones should be considered in the interpretation of any abnormal liver biopsy irrespective of clinical symptoms or biochemical investigations.

Immunological studies in the neonate of a mother with Addison's disease and diabetes mellitus.

In a baby born to a mother who had idiopathic (autoimmune) Addison's disease and gestational insulin-dependent diabetes, antibodies to adrenal cortex and to pancreatic islet cells were demonstrated in the cord blood and serum for at least 41 days. There was no clinical or objective evidence of adrenocortical failure or of disturbed carbohydrate tolerance in the baby.

Quantitative liver imaging using 131-I Rose Bengal as an index of liver function and prognosis.

A technique for assessing quantitatively hepatic function by direct measurement of liver parenchymal cell uptake of 131I Rose Bengal using a scintillation camera with a digital store and retrieval system is described. Ninety-four studies were performed on 84 patients with a variety of hepatic disorders over a two-year period, the diagnosis in each case being established by liver biopsy or laparotomy. The results were compared with the clinical, biochemical and histological assessment of the patients. A good correlation was found between the half-time for hepatic uptake of 131I Rose Bengal and the histological changes, as well as with clinical prognosis measured in terms of clinical improvement or deterioration to death. The rate of liver uptake was found to be a better index than the clearance of radioisotope from the blood and was superior to conventional biochemical investigations in both icteric and anicteric patients. The test was not shown to be of clinical value in discriminating between intra- and extrahepatic causes of jaundice. It is suggested that this technique may provide a safe and sensitive method for assessing the severity of liver dysfunction and also for monitoring clinical progress, especially in situations where liver biopsy may be unreliable or hazardous.