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Chloromethane was shown to react with human plasma and erythrocytes. Using 14C-CH3Cl, it was found that in plasma radioactivity was bound only by albumin. On hydrolysis the major reaction product was S-methylcysteine; small amounts of 1- and 3-methylhistidine were found. In plasma, the bound radioactivity corresponds to only 2–3% of the uptake measured using unlabelled CH3Cl, suggesting that other, unidentified volatile products are formed. In erythrocytes, approximately 40% of the uptake was bound by GSH forming S-methylglutathione. The reaction appeared to be enzyme-catalysed. Loss of thiol groups of plasma protein and erythrocytes and inhibition of oxygen uptake of erythrocytes could not be demonstrated. S-Methylglutathione was neither lost from erythrocytes during separation and washing, nor was it hydrolysed. It is postulated that some of the cases of anaemia reported following exposure to chloromethane may be due to lack of erythrocyte GSH.

This study evaluates the biochemical and hematological changes (hepatic renal and adrenocorticol functions and changes in platelet adhesiveness) resulting from the use of oxytocin prostaglandin (PG) E2 and PGF2alpha in labor induction. 75 patients from St. Marys Hospital in Manchester with gestational age of not less than 35 weeks were randomly assigned into 3 groups of 25 patients each for induction of labor with oxytocin PGE2 and/or PGF2a. Indications for induction included preeclempsia; postmaturity; an apparently small-for-dates fetus; presence of antibodies in Rh negative mother; and placental abruption occuring after 37 weeks gestation. Oxytocin was infused at a dose of 10 units/500 ml. of 5% dextrose starting with 1 mu/minute and doubling the dosage every half hour until labor was established. For PGF2a and PGE2 7.5 mg. and 0.75 mg. were respectively dissolved in 500 ml. of 5% dextrose. Starting dosages were 2.5 mcg/minute and 0.25 mcg/minute respectively; dosages were doubled if necessary after 30 and 90 minutes. Blood samples (pre-induction specimen during infusion and post-delivery specimen) were collected for full blood count and platelet adhesiveness studies at various periods of the study. Hematological analysis revealed no significant differences in pattern of response of red cell count hemoglobin or white cell count when oxytocin was compared with either prostaglandins. All 3 agents exhibited a similar rise in white cell count during labor. Difference in behavior between the different agents were mainly related to sodium chloride and water balance and to adrenocorticol responses as assessed by plasma cortisol levels. The analysis suggests that oxytocin caused water retention without affecting sodium balance. This was related to a significant decline in serum sodium level and a relatively high urinary osmolality. Neither of the prostaglandins exhibited such effects.

A commercial kit method (Technia Diagnostics) for the estimation of serum vitamin B12 claiming certain practical advantages was examined. Analytical and clinical performance were compared with a non-commercial radioisotope B12 method, previously compared to other commercial radioisotope B12 methods. The kit's analytical performance in our hands was satisfactory, although the within-batch precision and recovery of added cyanocobalamin were disappointing. Clinical performance was comparable with the non-commercial B12 method. Establishment of suitable reference ranges as a prerequisite to diagnostic use is apparent.

A simple, rapid radioimmunoassay for progesterone in unextracted serum is described. Cortisol is used to inhibit progesterone binding to corticosteroid binding globulin. The method has been optimised for the determination of progesterone in pregnancy sera or in the luteal phase of the menstrual cycle.

Five commercial kits for the determination of folate and six kits for the determination of vitamin B12 were investigated. Their performance has been compared with microbiological methods for the two vitamins and with a non-commercial radioisotopic method for B12. The results show the importance of the determination of the reference range for an individual laboratory for each method. The precision of the kits varied appreciably, as did their performance using specimens from patients with different haematological disorders. In particular, certain kits failed to detect all patients with pernicious anaemia. The relative accuracy of the kits was assessed. Various factors which should be taken into account in the final selection of a satisfactory kit are discussed.

Two patients with primary biliary cirrhosis who were increasingly incapacitated by xanthomatous neuropathy are described. Treatment with a low fat diet and cholestyramine was unhelpful but repeated plasmaphoresis by simple venesection in one and plasma exchange using an IBM blood cell separator in the other over a period of several months completely relieved the symptoms of the neuropathy, caused skin xanthomata to recede, and lowered plasma lipid levels in both patients. There was no evidence that this procedure was associated with any deleterious effects on the liver. The size of the cholesterol pool in xanthomata in one patient was estimated to be approximately 35 g, and from the plasma cholesterol response to plasmaphoresis at varying frequency it was suggested that the excess of cholesterol synthesis over degradation was less than 0·3 g/day in one patient and less than 0·4 g/day in the other. On the basis of the response in these patients it is suggested that the turnover rates of lipid pools are relatively slow in biliary cirrhosis and that cholesterol accumulation is more likely to be due to a reduced catabolic rate than to an increased synthetic rate of cholesterol. Plasmaphoresis or plasma exchange are useful methods of treatment for the rare patient afflicted by this resistant and distressing complication of biliary cirrhosis.

A revised scheme is described for evaluating automatic instruments used in clinical chemistry. Procedures are outlined for the assessment of mechanical and electrical features, and measurement of the accuracy and precision of individual units. Methods are given for the measurement of analytical precision, carryover, cross-contamination, accuracy, and linearity. The safety of equipment and methods of assessing costs are discussed, and the importance of subjective features is noted. The general principles of the evaluation scheme should be applicable to other types of equipment.

An atypical case of the malignant carcinoid syndrome, associated with multiple peptic ulcers, is described. The tumour cells were argyrophil but not argentaffin, and the tumour was found to contain 5-hydroxytryptophan (5-H.T.P.) but not 5-hydroxytryptamine (5-H.T.). This aberrant biochemical behaviour was associated with the virtual absence of 5-H.T.P.-decarboxylase from the tumour tissue. The tumour contained notable quantities of histamine.

Summary This paper describes the preparation and use of a control material (PlasCon) which may be aspirated in prediluted form to monitor the calibration of the Coulter Counter Model S Plus. A comparison study with two commercial preparations, and a study of the stability and between-batch reproducibility of PlasCon, show the material to be suitable for quality control of platelet counting.

Samples which are taken for the Quick one-stage prothrombin time estimation for the control of patients receiving oral anticoagulant treatment are by convention taken into liquid sodium citrate anticoagulant. Dried sodium citrate has been rejected on the grounds that excessive haemolysis causes activation of clotting factors and therefore falsely short clotting times. Tests were performed with both liquid and dried sodium citrate as an anticoagulant for prothrombin time and Thrombotest. No clinically significant difference between the values given by the two anticoagulants was observed.

Summary A radioimmunoassay for α1-fetoprotein in human maternal serum at 15–20 weeks' gestation using polyethylene glycol to separate bound and free antigen is described. A number of variables has been investigated to define optimal conditions for use at this gestation. The method gives results which agree with those from a double-antibody technique. It has good precision in the critical concentration range, and recoveries are satisfactory. The importance of including sufficient serum protein in the analytical system is stressed. There were systematic differences between three standard preparations of α1-fetoprotein, but three out of four antisera tested gave very similar results. The implications for screening for neural tube defects in early pregnancy are discussed.

Total serum amylase and its pancreatic and salivary isoamylase activities were studied in serum from 30 normal volunteers and 30 patients with liver disease. Isoenzyme analysis was performed by inhibitor assay and electrophoretic techniques. Six out of 30 patients had total serum amylase activities which exceeded the mean +/- 2 SD value for normal volunteers. The prominent type of isoenzyme was the pancreatic, except for patients with alcoholic cirrhosis. There was no evidence of any other type of isoenzyme by the electrophoretic method, nor was there an age-dependent isoamylase distribution.

Summary The main objectives of the evaluation were to: (1) assess accuracy and precision of cell recognition, (2) establish‘reference ranges’and compare with existing ranges, (3) assess machine reliability and suitability for normal working patterns. The accuracy and precision of the instrument were found to be acceptable, within the limits imposed by counting 100 cells in a wedge smear. Reference ranges compared well with established ranges with the exception of monocytes and eosinophils. The instrument was initially evaluated over a 12-week period and has been in routine use for 18 months during which time it has been found to be very reliable. It has fitted in with the laboratory working patterns without causing any changes in work flow.

Chloromethane reacted with rat and guinea pig brain, liver and kidney. Using 14C-CH3Cl with rat tissue homogenates, the bound radioactivity corresponded with the uptake in the liver and kidney but was lower in the brain. 14C-S-methylglutathione (GSMe) and 14C-S-methylcysteine (S-MeCys) were formed by liver, which did not hydrolyse 14C-GSMe, so that the 14C-S-MeCys must have been formed directly. Both reactions appear to be enzyme-catalysed. In the kidney and brain, 14C-S-MeCys and 14C-GSMe were formed and methylation of cysteine SH-groups in the mixed insoluble proteins was demonstrated. Traces of radioactivity were found in methionine in the kidney proteins. The kidney and brain homogenates hydrolysed 14C-GSMe. Rapid losses of radioactivity during processing in some kidney experiments suggest that volatile products are formed, but this is not due to fission of S-methyl groups of S-MeCys or GSMe. The level of binding was lower in heated tissues, especially in the water-soluble fraction. Inhibition of respiration of rat brain and inhibition of two thiol-dependent enzymes could not be demonstrated. It is suggested that loss of GSH and intracellular accumulation of GSMe may account for some of the clinical features of intoxication.

The content of folate activity precursors in washed red cells and the enzymatic plasma factor activity, necessary for the release of folate from the precursors, were studied in normal subjects and in patients with megaloblastic anaemia of pregnancy. Subjects with megaloblastic anaemia of pregnancy had a significantly reduced folate activity precursor content, and 14 subjects (58%) had significantly low plasma factor activity, which in at least four subjects may have been due to the presence of inhibitors. This study indicates that impaired activity of the plasma factor may play a part in the aetiology of megaloblastic anaemia of pregnancy.