Adjusting copper concentrations for caeruloplasmin levels in routine clinical practice.

BACKGROUND: An investigation on copper metabolism usually includes the measurement of serum levels of copper and caeruloplasmin. Using these levels, some laboratories derive levels of non-caeruloplasmin-bound copper (NCC); however, a considerable number of patients may show negative values, which is not physiologically possible. AIM: To derive an equation for adjusted copper in a manner similar to that widely accepted for adjusted calcium. METHODS: A linear regression equation for the relationship between caeruloplasmin and copper was used: [copper] (micromol/l) = 0.052x[caeruloplasmin] (mg/l). An equation for copper adjusted for caeruloplasmin was derived using this equation and the reference interval of 10-25 micromol/l for copper. RESULTS: The derived equation was [adjusted copper] (micromol/l) = [total copper] (micromol/l)+0.052x[caeruloplasmin] (mg/l)+17.5 (micromol/l). The adjusted copper concentrations on the 2.5th and 97.5th centiles were 12.7 and 21.5 micromol/l, respectively, with the population having a gaussian distribution. The relationship between NCC and the adjusted copper concentrations is linear and independent of caeruloplasmin concentration. CONCLUSION: Calculation of copper adjusted for caeruloplasmin uses the same variables as those for NCC. Accordingly, the problems that are caused by the lack of specificity of caeruloplasmin immunoassays are the same as those identified for NCC. This calculation, however, overcomes the negative values that are found in a considerable minority of patients with NCC, as well as age and sex differences in the caeruloplasmin reference interval. As the concept is already familiar to non-laboratory healthcare professionals in the form of calcium adjusted for albumin, this method is potentially less confusing than that for NCC.

Should all patients with unexplained anaemia be screened for chronic lead poisoning?

The global prevalence of lead poisoning is declining. However, the prevalence of lead poisoning in patients with either microcytic or normocytic anaemia is unknown. Blood samples from anaemic patients residing in south-east London without an obvious cause for anaemia had their blood lead concentration (BLC) analysed. A batch of 988 samples was analysed for BLC using atomic absorption spectroscopy. Median haemoglobin was 10.3 g/dL (range: 4.2-10.9) in females, 10.6 g/dL (range: 5.2-11.4) in males and 10.7 g/dL (range: 6.7-10.9) in children. Median BLC was 2.63 microg/dL (0.21-24.0 microg/dL; 95th centile 7.54 microg/dL). Fifteen samples (1.5%) had a BLC > 10.0 microg/dL, five samples (1%) > 15.0 microg/dL and one sample (0.1%) > 20.0 micrg/L. In the 106 children, median BLC was 2.34 microg/dL (0.5-14.5 microg/dL; 95th centile 6.12 microg/ dL). Only one child (14.5 microg/L) had a BLC > 10.0 pg/dL. There was a poor correlation between haemoglobin and BLC (r2 = 0.08). Routine screening for lead poisoning cannot be justified in all patients with unexplained anaemia, unless there is a history or clinical features to suggest lead toxicity. Additionally, we have shown that in this former high-risk area for lead exposure, there is a low point prevalence of significant lead poisoning, even in an anaemic population.

A case of lead poisoning due to snooker chalk.

A 3 year, 9 month old child with pica presented with a blood lead concentration of 1.74 micromol/l (360 microg/l). The source of poisoning was snooker chalk (lead content 7200 microg/g). She was treated with intravenous calcium disodium edetate chelation. Thirty months later her blood lead was 0.39 micromol/l (80 microg/l). This case illustrates the need to be vigilant for more unusual causes of lead poisoning in the home.

Clinical lead poisoning in England: an analysis of routine sources of data.

OBJECTIVE: To examine the occurrence of clinical lead poisoning in England based on routine sources of data. METHODS: Three routine data sources were examined, over different periods according to availability of data: (a) mortality for England, 1981-96; (b) hospital episode statistics data for England, for the 3 years 1 April 1992-31 March 1995; (c) statutory returns to the Health and Safety Executive under the reporting of injuries, diseases, and dangerous occurrences regulations (RIDDOR), also for the period 1 April 1992-31 March 1995. Also, analyses of blood lead concentrations carried out by the Medical Toxicology Unit, Guy's and St Thomas' Hospital Trust in London during the period 1 January 1991-31 December 1997 were examined. The analyses were performed both for industrial screening purposes and in response to clinicians' requests where lead poisoning was suspected. This is one of several laboratories carrying out such analyses in the United Kingdom. RESULTS: One death, of a 2 year old girl, was coded to lead poisoning in England during 1981-96. Analysis of hospital episode statistics data identified 83 hospital cases (124 admissions) over 3 years with any mention of lead poisoning, excluding two with admissions dating from 1965 and 1969. For these 83 cases the median hospital stay per admission was 3 days (range 0-115 days). Five were coded as having received intravenous treatment. Further clinical details of these cases beyond what is routinely recorded on the hospital episode statistics database were not available, except for blood lead concentrations in cases also identified on the Medical Toxicology Unit database. Eighteen cases (22%) were below 5 years of age of whom 10 (56%) came from the most deprived quintile of electoral wards. There was evidence to suggest spatial clustering of cases (p = 0.02). Six occupational cases were reported under RIDDOR in England during the period of study, two of whom were identified on the hospital episode statistics database. One further occupational case was identified on hospital episode statistics. Blood lead analyses for 4424 people carried out by the Medical Toxicology Unit (estimated at about 5% of such analyses in England over 7 years) found that among 547 children aged 0-4, 45 (8.2%) had a blood lead concentration in excess of 25 micrograms/dl, the action level in the United Kingdom for investigation, or removal of environmental sources of lead. At all ages, there were 419 (9.5%) such people, including 106 adults with no mention of industrial exposure. CONCLUSIONS: Both mortality and hospital admission ascribed to lead poisoning in England are rare, but cases continue to occur and some, at least, seem to be associated with considerable morbidity. Lead poisoning was confirmed as a probable cause of clinical signs and symptoms in only a small proportion of those in whom a blood lead concentration was requested. Where indicated, appropriate remedial action for the safe removal of environmental sources of lead should be taken.

Acute arsenic poisoning: absence of polyneuropathy after treatment with 2,3-dimercaptopropanesulphonate (DMPS).

Two men aged 19 and 21 years ingested 1 g and 4 g respectively from 3 kg of a white crystalline powder that they thought was a substance of abuse. It was later identified as almost pure arsenic trioxide. Both had nausea and vomiting and one developed acute renal failure. Each was treated with 2,3-dimercaptopropanesulphonate (DMPS), and made a full recovery with no evidence of prolonged renal or neurological impairment. The DMPS-arsenic complex is probably associated with lower penetration into the CNS and as a consequence treatment with DMPS may result in lower acute and chronic neurotoxicity than treatment with the currently standard recommended chelating agent dimercaprol (British Anti-Lewisite; BAL).

Safety and efficacy of acetarsol suppositories in unresponsive proctitis.

In a prospective open study, 10 patients with intractable proctitis were treated with acetarsol suppositories (250 mg b.d. for 4 weeks) and were monitored clinically, biochemically and toxicologically. Proctitis resolved symptomatically and sigmoidoscopically within 2 weeks in nine patients; one patient was unaffected. The only side-effect was of transient thrombocytosis in a single patient. Maximal blood and urinary arsenic concentrations occurred after 1 week's treatment with a total inorganic arsenic in the hazardous range in six patients; subsequent concentrations fell despite continuing therapy and at 4 weeks potentially hazardous values persisted in only two patients. Continued renal excretion and diminished absorption across an improved rectal mucosa is thought to be responsible for this paradox. Arsenic levels fell rapidly when acetarsol was withdrawn and were indistinguishable from pretreatment values within 4 weeks. Short-term acetarsol therapy offers a useful additional measure when local steroids have failed to control ulcerative proctitis; it appears to be safe and formal controlled comparisons with other therapeutic options are therefore legitimate.

Clinical features and therapy of acute thallium poisoning.

Severe acute thallium poisoning in a young man is described. He presented with transient loss of consciousness and paraesthesiae of finger tips and lips, with a blood thallium concentration of 5750 micrograms/l (levels above 200 micrograms/l are toxic). He rapidly lost limb sensation and power and later required temporary mechanical ventilation and nasogastric feeding. The neurological sequelae one year afterwards are a flaccid paraparesis, cerebellar ataxia and mental impairment. Immediate cardiovascular complications included hypertension, sinus tachycardia, ECG abnormalities and an episode of ventricular fibrillation. We were able to assess the relative merits of different methods advocated for enhancing thallium excretion. Oral Prussian blue, forced diuresis and haemodialysis were found to be the most effective: 2000 mg of thallium were eliminated over 20 days, 820 mg over 46 days and 225 mg over 25 days respectively by these methods. Haemofiltration was ineffective. Diethyldithiocarbamate, a chelating agent, brought about a rise in serum thallium concentration accompanied by clinical deterioration and its use should be abandoned.

Mercury concentration in cord blood.

The mean mercury concentration measured in cord blood from 51 inner city babies born at Guy's Hospital was significantly higher (37 nmol/l v 20 nmol/l) than that from 17 babies born at the Royal Devon and Exeter Hospital, which serves a more rural population.

Mercury poisoning after disc-battery ingestion.

A case is described of a 2-year-old girl who swallowed an alkaline disc battery containing mercuric oxide. Two days after ingestion it disintegrated in the stomach necessitating laparotomy to remove the battery casing and most of its contents. Postoperatively her blood mercury concentration rose to 340 micrograms/l and subsequently she developed small bowel obstruction due to adhesions. She was treated with dimercaprol but blood mercury concentrations did not fall until after a second laparotomy to relieve the obstruction and to remove residual mercury salts from the colon. The corrosive effects of swallowed disc batteries are well documented. The maximum blood concentration of mercury reported in this case is 17 times the 'acceptable level of mercury in the blood' and nearly double the highest level recorded previously after disc-battery ingestion. A policy for management of swallowed batteries is suggested.

Plasma mercury during prolonged acute renal failure after mercuric chloride ingestion.

Serial measurements of plasma mercury were made in a patient with severe and prolonged acute renal failure due to poisoning with mercuric chloride. An initial mercury concentration in whole blood of 1200 micrograms/l (6 mumol/l) was recorded, and recovery of renal function coincided with a fall in plasma mercury concentration to below 100 micrograms/l (0.5 mumol/l). The case demonstrates that survival and recovery of renal function is possible despite very high concentrations of mercury in the blood and oliguric renal failure of nearly six weeks' duration.