Prospective study of liver dysfunction in pregnancy in Southwest Wales.

BACKGROUND: Liver dysfunction in pregnancy has serious consequences. Its frequency and characteristics have not been systematically documented in Britain. We have prospectively determined incidence, causes, and outcome of liver dysfunction in pregnancy in an obstetric unit in Southwest Wales, UK. METHODS: A central laboratory identified all abnormal liver tests (bilirubin >25 micro mol/l, aspartate transaminase >40 U/l, or gamma glutamyl transpeptidase >35 U/l) from patients in antenatal clinics and wards of an obstetric unit serving a population of 250 000. Patients with abnormal liver tests were assessed and followed throughout and after pregnancy [corrected]. Medical advice was provided to obstetric teams. FINDINGS: There were 4377 deliveries during the 15 month study. A total of 142 patients had abnormal liver tests. There were 206 contributing diagnoses, the great majority being pregnancy specific. Among the most important were pre-eclampsia (68), HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome (30), obstetric cholestasis (23), hyperemesis gravidarum (11), acute fatty liver of pregnancy (five), and hepatic infarct (one). Sepsis, postoperative factors, and placental pathology (51) were not uncommonly responsible but incidental or pre-existing hepatobiliary disease was infrequent (17). Sixty five patients were delivered early by induction or caesarean section because of liver dysfunction. Despite substantial liver related morbidity, there were no maternal deaths and only two intrauterine deaths. CONCLUSIONS: Liver dysfunction was seen in 3% of deliveries during a 15 month prospective study and was usually directly related to pregnancy with spontaneous recovery in the puerperium. Incidence of the most serious conditions, acute fatty liver of pregnancy and HELLP syndrome, was much greater than previously reported. Profound effects on maternal and infant health were observed but close medical and obstetric collaboration ensured low mortality.

The causes of obvious jaundice in South West Wales: perceptions versus reality.

AIMS: (1) A prospective analysis of clinically obvious jaundice (bilirubin >120 micromol/l) in South Wales to determine accuracy of diagnosis, referral pattern, treatment, and outcome. (2) To compare British gastroenterologists' and local general practitioners' perceptions of common causes of jaundice with our study findings. METHODS: Over a seven month period all patients with bilirubin >120 micromol/l (excluding neonates with physiological jaundice) were identified by a biochemistry laboratory serving three general hospitals and the community. Clinical data were recorded prospectively. Sixty nine consultant gastroenterologists and 67 local general practitioners (GPs) were asked to cite the commonest causes of bilirubin >120 micromol/l in their experience. RESULTS: A total of 121 patients were identified of whom 95 were admitted to hospital because of jaundice, 22 developed jaundice while in hospital, and four remained in the community. Causes of jaundice were: malignancy 42, sepsis/shock 27, cirrhosis 25, gall stones 16, drugs 7, autoimmune hepatitis 2, and viral hepatitis 2. One in five was wrongly diagnosed, often as viral hepatitis. Although 30% were under surgical care only 4% required surgery. Overall mortality was high (31%) and greatest in sepsis/shock (51%). Gastroenterologists and GPs both perceived malignancy and gall stones to be the commonest causes of marked jaundice followed by viral hepatitis and cirrhosis; sepsis/shock was hardly mentioned. CONCLUSIONS: There are important discrepancies between gastroenterologists' and GPs' perceptions of likely causes of jaundice and the actual causes we have shown. In particular, sepsis/shock is common in hospital practice but is overlooked whereas viral hepatitis is rare but perceived as common and overdiagnosed. Gall stones usually cause mild jaundice with bilirubin levels less than 120 micromol/l. Many patients are referred to surgical services for historical reasons yet rarely require surgery and are usually treated by physicians or endoscopists.

A prospective study of the causes of notably raised aspartate aminotransferase of liver origin.

BACKGROUND AND AIMS: To ascertain the causes of raised aspartate aminotransferase (AST) presumed to be of hepatic origin in two hospitals and the local community served by a centralised biochemistry laboratory. METHODS: From June 1996 to February 1997 all patients with AST greater than 400 U/l were identified by the biochemistry laboratory; the patients' clinical records were studied to determine the diagnosis, the clinical outcome, and whether the raised AST and its significance had been noted. RESULTS: A total of 137 patients with a hepatic cause for the raised AST were found. The cause of the raised AST was hepatic ischaemia/hypoxia in 68, pancreatobiliary disease in 33, primary hepatocellular disease in 23, hepatic malignancy in five, and hepatic haematoma in one. In seven patients the diagnosis was unclear. The overall mortality was high (22%) with the highest mortality in the hepatic ischaemia group (37%). The recording and interpretation of the causes of raised AST was poor with only 48% having the correct diagnosis. In 38% the raised AST was apparently not noticed by the attending clinicians. CONCLUSIONS: The commonest cause of a hepatitis like biochemical picture was hepatic hypoxia (50%) followed by pancreatobiliary disease (24%). Drug induced hepatic necrosis (8.8%) was uncommon and viral hepatitis was rare (3.6%). AST concentrations returned towards normal most rapidly in patients with hepatic hypoxia and calculous biliary obstruction. Hepatitis, viral or otherwise, is an uncommon cause of a typical hepatitic biochemical result in this community.

The development of a technique to measure bone aluminium content using neutron activation analysis.

The accumulation and toxicity of aluminium in patients with chronic renal failure is a well recognized hazard, and there is a need for a non-invasive technique to assess Al tissue load in these patients. The technique of in vivo neutron activation analysis, using a thermal neutron beam from a reactor, has been employed by previous workers, who measured Al in the hand with a detection limit of 0.4 mg for a dose equivalent of 20 mSv. However, the application of this technique is restricted by the very limited availability of nuclear reactors. We report the modification of an existing 252Cf-based instrument and construction of a shielded, high-efficiency counting system for the in vivo measurement of Al in the hand. Phantoms containing tissue-equivalent solutions of Ca, P, Na and Cl with various Al loadings were used for validation of the technique. The Al/Ca ratio in the hands of seven patients with renal failure was measured using a cyclic activation technique to compensate for the relatively low neutron output of the 252Cf source, and a detection limit of approximately 2.2 mg Al was achieved for a dose equivalent of 36 mSv. The results were compared with the Al content of iliac crest bone biopsy specimens measured using electrothermal atomic absorption spectrophotometry.

In vivo measurements of cadmium and lead in occupationally-exposed workers and an urban population.

This paper reports the preliminary findings of a survey of lead and cadmium body burdens in a nonoccupationally exposed population in Swansea, Wales, using the techniques of in vivo neutron activation and X-ray fluorescence analysis. Some measurements on an occupationally cadmium-exposed group are also included. The results confirm the association between cadmium and smoking and bone lead and age. The in vivo measurements demonstrate a degree of comparability with other data, which supports the further detailed analysis of the relationships between body burden and exposure, on the one hand, and possible health effects on the other.

Comparison of digoxin analysis by EMIT with Immophase and Dac-Cel radioimmunoassay.

The results obtained by an enzyme multiplied immunoassay kit, EMIT, for the measurement of serum digoxin concentration were compared with those from two radioimmunoassay kit methods, Immophase and Dac-Cel. Patients' sera were used to study the correlation between the methods, and three quality control sera with low, intermediate, and high digoxin concentrations were used to study individual method precision. The coefficients of correlation between the three methods varied between 0.915 and 0.951 for serum drug concentrations up to 4.5 nmol/l. There were statistically significant differences between the means of the patients' samples for each method. Precision was acceptable for each method: within-batch percentage coefficient of variation (%CV) less than 8, between-batch %CV less than 10, except for Dac-Cel at low concentration %CV = 18.6. The time taken for the analysis of a batch of 10 samples was between 1.5 and 2 hours, depending on the method.

Low leucocyte ascorbic acid levels and corneal ulceration.

The leucocyte ascorbic acid levels were determined in six patients with infected corneal ulcers. These levels were significantly lower than in a control group matched for age and sex. The potential role of Corynebacteria as pathogens is discussed.

An evaluation of the Jeol Clinalyzer.

The Jeol Clinalyzer was evaluated over a period of 15 weeks. The operating principles are briefly described. The functions of the mechanical components were tested and assessments made of the instrument's safety and reliability. The mechanical and electrical reliability of the instrument was excellent and the pumps and spectrophotometer gave good accuracy and precision. Between-batch precision of the analytical methods was good for urea, protein and bilirubin and acceptable for alkaline phosphatase and aspartate transaminase. There was a poor relative accuracy for alkaline phosphatase and aspartate transaminase and some proportional inaccuracy for urea and bilirubin.

A survey of weighing performance in clinical biochemistry laboratories.

Results of a survey of accuracy and precision of weighing in a sample of clinical biochemistry laboratories in the U.K. are reported. 101 laboratories each carried out eight weighings. 94% of weighings were subject to errors of not more than 1.7 mg at the 2 g level and not more than 1.0 mg at the 100 mg level. However, 9% of the laboratories produced results which were consistently subject to larger errors.

The quality control of alkaline phosphatase determinations with placental phosphatase.

Human placenta has been recommended as the source of the alkaline phosphatase used for the preparation of control or reference materials. The effect of certain inhibitors, which may be present in the reagents, on control materials containing the placental isoenzyme, is shown to differ significantly from their effect on the isoenzymes in patient's sera. This finding indicates that if control materials are used which contain only human placental alkaline phosphatase, changes in accuracy resulting from differences in reagent quality may be missed, or alternatively a change in accuracy may be indicated by the quality control results which does not apply to the patient's sera.