[From laboratory to practice: counseling with clinicians].

The provision of medical laboratory services is a key element in diagnostic and treatment. The care of analytical quality remains in focus of attention. The interest to pre-analytical quality increased. However, alongside with it quality of post-analytical stage and such its significant element as support of timely and effective application of laboratory results in interest of patient has great importance. The purpose of study was to consider approaches to development of this aspect of medical laboratory practice and to demonstrate the modes which proved their effectiveness.

Guidelines for laboratory analyses for poisoned patients in the United Kingdom.

To enable consistency of investigation and the establishment of best practice standards, consensus guidelines were formulated previously by the UK National Poisons Information Service and the Association for Clinical Biochemistry. These joint guidelines have now been updated to reflect current best practice. The types of laboratory investigation required for poisoned patients are categorized as either (a) essential common laboratory investigations or (b) specific toxicological assays, and also as either (i) common or (ii) specialist or infrequent. Tests in categories (a) and (bi) should be available 24 hours per day, with a maximum turnaround time of 2 h. For the specialist assays, i.e. category (bii), availability and turnaround times have been specified individually. The basis for selection of these times has been clinical utility. The adoption of these guidelines, along with the use of the National Poisons Information Service (0844 8920111) and its online poisons information resource TOXBASE(®) (www.toxbase.org) enable the poisoned patient to receive appropriate, 'best practice' investigations according to their clinical needs and will avoid unnecessary investigations.

Best practice in primary care pathology: review 4.

This fourth best practice review examines four series of common primary care questions in laboratory medicine are examined in this review: (1) safety monitoring for three common drugs; (2) use of prostate-specific antigen; (3) investigation of vaginal discharge; and (4) investigation of subfertility. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of the guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most of them are consensus based rather than evidence based. They will be updated periodically to take account of new information.

Best practice in primary care pathology: review 5.

This fifth best practice review examines three series of common primary care questions in laboratory medicine: (1) minor liver function test abnormalities; (2) laboratory monitoring of patients receiving lithium; and (3) investigation of possible venous thromboembolism. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus-based rather than evidence-based. They will be updated periodically to take account of new information.

Troponin for prediction of cardiovascular collapse in acute colchicine overdose.

The use of colchicine, a treatment for acute gout and familial Mediterranean fever, is limited by its toxicity. A relatively low dose of colchicine may be fatal. After a colchicine overdose, monitoring should include 6-12 hourly serum troponin measurements. A rising troponin level predicts cardiovascular collapse and is an indication for more intensive management.

Recurrent vesical calculi, hypercalciuria, and biochemical evidence of increased bone resorption in an adult male with paraplegia due to spinal cord injury: is there a role for intermittent oral disodium etidronate therapy for prevention of calcium phosphate bladder stones?

STUDY DESIGN: Clinical case report with comments by colleagues from Sweden, Poland, Spain, Brazil, Japan, Belgium and Switzerland. OBJECTIVES: To discuss the role of disodium etidronate therapy for prevention of calcium phosphate vesical calculi in persons with spinal cord injury, who have hypercalciuria and biochemical evidence of increased bone resorption. SETTING: Regional Spinal Injuries Centre, Southport, UK. METHODS: A 21-year-old male sustained paraplegia (T-10; ASIA scale: A) in a road traffic accident in June 2001. He had an indwelling urethral catheter until the end of August 2001, when he started self-catheterisation. He developed bladder stones and electrohydraulic lithotripsy (EHL) was performed in May 2002. All stone fragments were removed. Recurrence of vesical calculi was noted in October 2002. These stones were fragmented by lithoclast lithotripsy in two sessions, in December 2002 and February 2003; all stone fragments were removed at the end of the second session. This patient reverted to indwelling catheter drainage when vesical calculi recurred. In September 2003, X-ray of the abdomen showed recurrence of vesical calculi. By February 2004, the stones had increased in size and number. EHL of vesical calculi was again performed in April 2004. Complete clearance was achieved. RESULTS: A 24-h urinalysis detected hypercalciuria--18.7 mmol/day (reference range: 2.5-7.5). Biochemical analysis of vesical calculus revealed calcium phosphate (85%) and magnesium ammonium phosphate (15%). Plasma C-terminal telopeptide (CTX) was increased - 1.06 ng/ml (reference range: 0.1-0.5 ng/ml). Free deoxypyridinoline/creatinine ratio (fDPD/Cr) in urine was also increased - 20.2 (reference range: 2.3-5.4). In April 2004, this patient was prescribed disodium etidronate 400 mg day. Nearly 3 months after commencing therapy with etidronate, plasma CTX decreased to 0.87 ng/ml. fDPD/Cr in urine also decreased to 12.4. After 4 months of etidronate therapy, 24-h urinary calcium excretion had decreased to 6.1 mmol/day. CONCLUSION: Etidronate (400 mg daily) is a very effective inhibitor of calcium phosphate crystallisation. Etidronate decreased urinary excretion of calcium, an important factor in prevention of calcium phosphate bladder stones. Etidronate therapy is not a substitute for other well-established methods for prevention of vesical calculi in spinal cord injury patients, for example, large fluid intake, avoiding long-term catheter drainage. Intermittent therapy with etidronate may be considered in selected patients, in whom hypercalciuria persists after instituting nonpharmacological therapy for an adequate period, for example, early mobilisation, weight-bearing exercises, and functional electrical stimulation. However, possible side effects of etidronate, and the fact that etidronate is not licensed in United Kingdom for prevention of urolithiasis, should be borne in mind.

Laboratory analyses for poisoned patients.

Guidelines on the appropriate availability and use of laboratory analysis have been produced by the National Poisons Information Service and the Association of Clinical Biochemists and are published in this issue. These are intended to support the consistent and high quality investigation of the poisoned patient.

External quality assessment of laboratory performance in analysis of toxicological cases.

A mean of 44 members of the United Kingdom national external quality assessment scheme (UKNEQAS) for toxicology reported analytical findings on 10 toxicological cases circulated between December 1995 and February 2000. Material distributed usually consisted of a 5ml blood and a 20ml urine sample simulated by quantitative addition of drugs and their metabolites to material donated by volunteers and patients. The samples were accompanied by a brief outline of the circumstances surrounding the case. Laboratories were requested to report their analytical findings, list methods of analysis, and provide interpretation of their findings. The mean overall success rate for identification of drugs or their pharmacological group was 76%, failure being largely by laboratories providing an immunoassay-based screening service for a fixed range of drug groups. The latter laboratories indicated that cases would be referred to regional toxicology centres for further investigation or confirmation. The coefficient of variation of measurements was <7% for routine analytes, such as ethanol and paracetamol, but 26-44% for tricyclics and opiates. There were 3% false positive reports. The quantity and content of interpretative comment provided by the laboratories was very variable. A number provide nothing in addition to the analytical result.

A survey of extraction techniques for drugs of abuse in urine.

Sixty nine participants in the United Kingdom national external quality assessment scheme for drugs of abuse in urine reported details of their sample extraction technique by questionnaire. Laboratories were categorised by differences in technique and their analytical test results compared for samples containing D-amfetamine 0.4 (4) and 0.8 (3) mg/l, morphine 0.4 (4) and 0.8 (4)mg/l, and benzoylecgonine 0.15/0.2 (2) and 0.45/0.5 (4) mg/l. Values in parentheses are numbers of samples. For amfetamine, there was no significant difference in the frequency of true positive results between liquid-liquid or solid phase extraction and the Toxi-Lab A system at 0.8 mg/l. Toxi-Lab A gave significantly fewer positives when operating below its specified threshold at 0.4 mg/l. Paradoxically, laboratories using >5 ml urine volume performed less well. Acidification of the extract before volume reduction gave significantly more true positives. For extraction of morphine, solid phase systems significantly outperformed both liquid-liquid and the Toxi-Lab A system at both 0.8 and 0.4 mg/l. No significant differences between extraction techniques were demonstrated for analysis of benzoylecgonine.

Use of microalbuminuria as a predictor of outcome in critically ill patients.

We have investigated the use of microalbuminuria as a predictor of outcome in a pilot study involving 50 critically ill patients in a six-bed hospital intensive care unit (ICU). Urinary microalbumin:creatinine (M:Cr) ratios measured only 6 h after admission to the ICU demonstrated a significant difference (P = 0.01) between survivors and non-survivors, allowing rapid identification of patients at increased risk of developing organ failure and at greater risk of death. This work suggests that earlier identification of these patients using a rapid, simple, inexpensive biochemical test is possible; if confirmed in a larger study, it may be that clinical interventions can be targeted at those most likely to benefit.

Measures of total free radical activity in critically ill patients.

OBJECTIVES: To examine the role played by free radicals during the initial phase of critical illness in patients on an Intensive Care Unit (ICU). DESIGN AND METHODS: Serum total antioxidant status (TAS) and uric acid (UA) levels were measured in 50 patients over 18 hours to represent the initial stage of critical illness. Clinical scoring systems (APACHE II and multiple organ dysfunction scores) were used to assess the degree of organ dysfunction. Outcome was assessed according to patient survival (survivors, n = 36; non-survivors, n = 14). RESULTS: Serum TAS was higher in non-survivors; a similar finding was demonstrated for serum UA. Levels of both biochemical markers were associated with the degree of organ function and with higher antioxidant and UA levels present in patients with more severe organ dysfunction. In addition, serum UA was significantly correlated to serum TAS and probably accounted for much of the antioxidant activity observed. CONCLUSIONS: The increased TAS and UA levels observed may simply be a response to the degree of renal dysfunction observed as those patients with worse renal function had higher TAS and UA levels. In conclusion, measurement of serum TAS appears to be a reflection of UA concentration and results should be interpreted with caution particularly in patients who have renal dysfunction.

Detection and identification of morphine in urine extracts using thin-layer chromatography and tandem mass spectrometry.

The application of tandem mass spectrometry to the analysis and identification of morphine following thin-layer chromatography is described. FAB-mass spectrometry and mass spectrometry-mass spectrometry were performed following chromatography on silica gel high-performance thin-layer chromatography plates. The successful application of this simple methodology to a urine extract suggests that this approach has practical utility for confirming the identity of abused drugs detected by thin-layer chromatography.

Routine analysis of amphetamine class drugs as their naphthaquinone derivatives in human urine by high-performance liquid chromatography.

We describe a simple HPLC method which is suitable for the routine confirmation of immunoassay positive amphetamine urine samples. The precolumn derivisation method employing sodium naphthaquinone-4-sulphonate was found to have adequate sensitivity, selectivity and precision for the measurement of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethylamphetamine (MDEA) at 500 microg/l cutoff level for confirmatory analysis of amphetamines in urine. The specificity of the method is enhanced by detecting the peaks at two different wavelengths. The ratios of the peak heights measured at the two wavelengths were different for each of the 5 amphetamines analysed. There was no interference from other phenylethylamine analogues that are commonly found in "over the counter" preparations. The HPLC method is compared to a commercial TLC system for detecting amphetamines in urine of drug abusers attending drug rehabilitation programmes. The HPLC confirmatory method described is a viable alternative to GC or to the more complex and costly GC-MS techniques for confirming amphetamine, methamphetamine, MDMA, MDA and MDEA in urine of drug abusers especially when used in a clinical care setting.