Limitations of non-ceruloplasmin-bound copper in routine clinical practice.
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Ceruloplasmin↗
Biomedical subjects
T M Reynolds
Publications and source records attributed to T M Reynolds.
The MDRD formula and validation.
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Chronic Disease↗
Best practice in primary care pathology: review 6.
This sixth best practice review examines four series of common primary care questions in laboratory medicine: (1) laboratory monitoring in hypertension and heart failure abnormalities; (2) markers of inflammatory joint disease; (3) laboratory investigation of chronic diarrhoea; and (4) mumps and chickenpox. 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.
Arthritis↗
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.
Chlamydia Infections↗
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.
Ceruloplasmin↗
Weight correction of MoM values: which method?
BACKGROUND: Adjusting maternal serum markers for maternal weight is considered to be a standard practice when screening for pregnancies associated with Down's syndrome. The choice of model for taking maternal weight into account is, however, rarely explicitly evaluated. METHOD: The relationship between the maternal serum markers alphafetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3), determined with the Beckman Coulter access reagents and maternal weight was investigated in a cohort of 752 Belgian women being screened for pregnancy associated with Down's syndrome. Two different models (the log-linear equation and the linear-reciprocal equation) were used to determine the relationship between the serum markers and maternal weight. RESULTS: A significant relationship between log(10) multiples of median (MoM) values and weight (kg) was obtained for all markers, and the log-linear model had higher coefficients of determination (r(2)) when compared with the linear-reciprocal model. Weight correction with either method achieved the optimum effect that the correction factor for a woman with a population median weight of 65.5 kg was not significantly different from 1. Simulated weight-corrected MoM values with the two approaches were compared and variation was estimated. The mean difference between the weight-corrected MoM values calculated by the two methods was 7.8% (SD 4.3%) for AFP, 14.0% (4.4%) for HCG and 5.9% (3.2%) for uE3. This resulted in a difference in risk estimate of 1.66-5.34% for Down's syndrome owing to weight correction algorithm differences in women of median weight. CONCLUSION: The log-linear weight correction approach was shown to be marginally more effective by a goodness-of-fit analysis. Differences in weight-corrected MoM values estimated with the two approaches are highly significant (p<0.0001, Wilcoxon's paired sample test), but the effect on risk calculation was not significant. It was observed that the changes in risk became significant the more the MoM correction factors deviated from 1.
Biomarkers↗
Assessment of a prognostic biochemical indicator of nutrition and inflammation for identification of pressure ulcer risk.
BACKGROUND: Pressure ulcers represent a major cost to the healthcare systems of the world but preventative measures are expensive and could be better targeted. Current risk screening mechanisms are often subjective and could be improved. AIMS: To evaluate whether a biochemical assessment tool (Prognostic Inflammatory and Nutritional Index; PINI) based on measurement of albumin, alpha1-acid glycoprotein, C-reactive protein, and prealbumin is of value in estimating the prognosis of patients with pressure ulcers of European Pressure Ulcer Advisory Panel grade 1 and above. METHODS: Serum samples were collected from patients participating in a clinical trial of a pressure ulcer preventing mattress. These were analysed for the markers listed above and the PINI calculated. PINI was then evaluated against patient outcome. RESULTS: A statistically significant difference between PINI values in patients whose pressure ulcers improved and those whose ulcers worsened was found in parametric testing, but significance was not achieved in non-parametric testing. A receiver operating characteristic plot showed the PINI was superior to chance in estimating prognosis. CONCLUSIONS: The PINI appears to offer a potential route to improving pressure ulcer risk estimation and thus allocation of scarce equipment to improve prevention.
Biomarkers↗
Best practice in primary care pathology: review 3.
This best practice review examines four series of common primary care questions in laboratory medicine: (i) "minor" blood platelet count and haemoglobin abnormalities; (ii) diagnosis and monitoring of anaemia caused by iron deficiency; (iii) secondary hyperlipidaemia and hypertriglyceridaemia; and (iv) glycated haemoglobin and microalbumin use in diabetes. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis 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 of the recommendations are based on consensus rather than evidence. They will be updated periodically to take account of new information.
Anemia, Iron-Deficiency↗
National Institute for Health and Clinical Excellence guidelines on preoperative tests: the use of routine preoperative tests for elective surgery.
Clinical Guideline CG3 from the National Institute for Health and Clinical Excellence (NICE) makes recommendations on appropriate clinical practice in preoperative testing for elective surgery. Unfortunately, there is minimal evidence on which the guidelines could be based and therefore they were constructed on the basis of professional opinion. This resulted in the construction of a decision matrix of Byzantine complexity built on foundations of sand: surgical risk is estimated using an unvalidated ad hoc risk estimation method; anaesthetic risk is estimated using the American Society of Anesthesiologists (ASA) risk method that has been demonstrated to be incapable of generating consistent risk assessments. The resultant matrix may be suitable for use as a template for future research, but is extremely complex and inadequately rigorous for routine use.
Academies and Institutes↗
The role of CA125 in clinical practice.
BACKGROUND: CA125 is a high molecular weight glycoprotein, which is expressed by a large proportion of epithelial ovarian cancers. The sensitivity and specificity of CA125 are poor and there are no guidelines produced by the Royal College of Pathologists or the Association of Clinical Biochemists to aid clinicians and laboratories in its most appropriate use. AIM: To identify the patient population having a CA125 measurement and to determine its contribution to individual patient management. METHODS: A retrospective case note audit looking at patients who had a CA125 measurement performed between April 2000 and April 2002. RESULTS: The study comprised 799 patients; 751 (94%) were female and 48 (6%) male; 221 (29%) females and 22 (46%) males had an abnormal result. CA125 was mainly used to investigate a wide range of signs and symptoms, and few tests were for follow up or screening of ovarian cancer. In female patients having a CA125 for suspicion of malignancy/ovarian cancer, only 39 (20%) of the abnormal results were caused by ovarian cancer. False positive results were largely caused by another malignancy (48 cases; 26%), benign ovarian disease (26 cases; 14%), and benign gynaecological conditions, particularly leiomyomas (18 cases; 9%). The specificity of CA125 for ovarian cancer increased with concentrations >1000 kU/litre. CONCLUSIONS: These results confirm the high false positive rate and poor sensitivity and specificity associated with CA125. The substantial inappropriate usage of CA125 has led to results that are useless to the clinician, have cost implications, and add to patient anxiety and clinical uncertainty.
Adult↗
ACP Best Practice No 181: Chemical pathology clinical investigation and management of nephrolithiasis.
Renal stones have afflicted humans for millennia but there is still no solution to this problem. This review discusses the laboratory and metabolic aspects of the clinical management of patients with renal stones, both primary and secondary in origin. First, non-pharmacological interventions such as increased fluid intake, decreased protein consumption, dietary changes in sodium, calcium, oxalate, potassium, purine, vitamins, and essential fatty acids are considered. Then specific pharmacological treatment to modify urine calcium, oxalate, urate, citrate, and acidity are considered. Finally, more unusual types of stone are examined.
Acidosis, Renal Tubular↗
Using image analysis to determine cause, severity, status and healing prognosis in wound management.
It is vital to evaluate the visual appearance of a wound when considering potential management options. However, where human vision lacks precision, image analysis has been shown to offer a more reliable method of assessment.
Color↗
The number of unexpected HbA variants may be a greater problem in routine practice than is generally realized.
BACKGROUND: The majority of variant and abnormal haemoglobins are clinically silent but may not be biochemically silent when it comes to HbA1c estimation. CASE REPORT: We describe several cases in which there were problems in the determination of HbA1c for monitoring diabetes in patients that would not normally be classified as being at risk. Four of these cases were sufficiently unusual to warrant individual publication but all came from a very restricted geographical area with a population of only approximately 500,000. The significance of this is not that variant haemoglobins affect HbA1c analysis but that the occurrence of unexpected/unusual variant haemoglobins may be more frequent than most clinicians would expect, considering that only a small proportion of the basal population are diabetic and have their HbA1c monitored. Differences will exist between different areas due to differences in both the prevalence of variants and the analytical methods employed. CONCLUSIONS: Consequently, we propose greater interaction between diabetologists and the laboratory in an attempt to identify these clinically but not biochemically silent variants to achieve a true estimation of the glycaemic control in affected patients.
Adult↗
Does activity in research correlate with visibility?
BACKGROUND: A previous survey has highlighted the fact that most individuals in chemical pathology identifiable from specialist society membership failed to publish material in Medline cited journals during a five year period. It could be considered that published research that is not cited in other work is not useful unless it has achieved visibility, as demonstrated by citation in another research publication. AIMS: To determine whether the frequency of research publication is associated with research visibility. METHODS: A random selection from the previous survey was investigated to determine whether the frequency of research publication is associated with research visibility. RESULTS: There was a logarithmic relation between the frequency of publication and visibility, with an increasing probability of citation as publication frequency increases. CONCLUSIONS: If academic activity is to survive then individuals must stay active in research; this requires a continuing commitment to a tradition of support for individuals at all stages of their careers engaging in research.
Authorship↗
The casino of life.
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Clinical Laboratory Information Systems↗
Chemical pathology and the new contract for GPs.
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Contracts↗
Statin precipitated lactic acidosis?
An 82 year old woman was admitted with worsening dyspnoea. Arterial blood gases were taken on air and revealed a pH of 7.39, with a partial pressure of CO2 (pCO2) of 1.2 kPa, pO2 of 19.3 kPa, HCO3 of 13.8 mmol/litre, and base excess of -16.3 mmol/litre: a compensated metabolic acidosis with hyperventilation induced hypocapnia, which is known to be a feature of lactic acidosis. There was also an increased anion gap ((Na140 + K4.0) - (Cl 106 + HCO3 13.8) = 24.2 mEq/litre (reference range, 7-16)), consistent with unmeasured cation. Lactate was measured and found to be raised at 3.33 mmol/litre (reference range, 0.9-1.7). After exclusion of common causes of lactic acidosis Atorvastatin was stopped and her acid-base balance returned to normal. Subsequently, thiamine was also shown to be deficient. The acidosis was thought to have been the result of a mitochondrial defect caused by a deficiency of two cofactors, namely: ubiquinone (as a result of inhibition by statin) and thiamine (as a result of dietary deficiency).
Acidosis, Lactic↗
Down's syndrome screening is unethical: views of today's research ethics committees.
BACKGROUND: Screening for Down's syndrome forms part of routine obstetric practice. Ethical considerations relating to genetic screening form a major part of the workload of research ethics committees. This study investigated the attitudes of research ethics committee members to several conditions varying in clinical severity and prognosis, including Down's syndrome. METHODS: The members of 40 randomly chosen research ethics committees were surveyed. A simple questionnaire comprising 19 clinical scenarios based around four "clinical" conditions was designed to review conditions that were potentially embarrassing, affecting life span but not mental ability, premature death, and intellectual impairment with a risk of neonatal cardiac defects (Down's syndrome). Screening tests with different degrees of effectiveness were described and the diagnostic test descriptions ranged from having no risk to an unaffected fetus to causing spontaneous abortion of two normal fetuses for each affected fetus identified. Replies were graded on a scale of 1 to 5. RESULTS: Seventy seven replies were received from 28 different research ethics committees. Screening was supported for treatment of a life threatening condition (95% in favour) but screening for conditions of a slight increase in premature death (14% in favour) or cosmetic features (10% in favour) were considered unethical. Views were ambiguous (49% in favour) about conditions involving significant shortening of lifespan. Down's syndrome screening was considered more ethical when described as a serious condition (56% in favour) than when the clinical features were described (44% in favour). Once increased rates of spontaneous abortion on confirmatory testing were added, 79% (21% in favour) and 86% (14% in favour) stated that screening was unethical (for "serious" and "clinical features" descriptions, respectively). CONCLUSIONS: Down's syndrome screening raises ethical concerns about genetic testing in general that need to be dealt with before the introduction of any prenatal screening test.
Attitude↗