bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of incorrect gestational dating on Down's syndrome and neural tube risk assessment
Authors: Millner S N
Published: October 2002

Down's syndrome risks are estimated between 15 and 20 completed weeks' gestation (cGW) using an algorithm involving maternal age and serum x-fetoprotein (AFP), chorionic gonadotrophin and unconjugated oestriol levels, each expressed as a multiple of the median level (MoM) at the cGW. The AFP MoM itself is the basis for screening for open neural tube defects (oNTD). Because medians change during this period, gestational dating must be accurate so that appropriate medians are used. A calculated Down's syndrome risk >1:380 at term is generally considered to indicate a 'high-risk' pregnancy. This study focused on 378 patients with reported risk ≤1:500 based on physician-supplied cGW (and hence considered at 'low risk' for Down's syndrome) to determine the effect of common 1-2-week dating errors on risk estimates. Using the original analytical data, each patient's risk was recalculated for each week over the 15-20 weeks, and classified into three categories: <1:380 'low'; 1:380-1:100 'moderate'; and >1:100 'high'. Advancing originally 'low-risk' patients by one week increased the risk by 1·09-14·1 times (median 3·18, mean 3·60); 46 (12·2%) became 'moderate' and 2 (0·5%) became 'high' risk. Advancing by two weeks increased risks 1·58-60·5 times (median 10·03, mean 12·04); 131 (36·5%) became 'moderate' and 39 (10.9%) became 'high' risk. Predictably, oNTD screening results also were affected. Although 1-2 week differences in AFP medians had little effect on most patients in this study sample, some who originally were oNTD negative became oNTD positive, whereas others who had been oNTD positive became screen negative. Thus, in many cases, a 1-2 week dating error may have only minimal effect on the estimated risks for chromosome or neural tube defects, but in other cases the effect of such an error would be significant.
Oxidative stress in haemodialysis: immediate changes caused by passage of blood through the dialyser
Authors: Rao P V L N Srinivasa , Dakshinamurty K V , Saibaba K S S , Sheela R B , Venkataramana G , Sreekrishna V , Ambekar J G , Jayaseelan L
Published: October 2002

Oxygen free radicals have been implicated in the long-term complications of maintenance haemodialysis. Studies that have probed into the mechanisms of oxygen radical production have implicated the bio-incompatibility of dialysis membranes. Changes between the arterial (inlet) and venous (outlet) points of a dialyser may give a better picture of blood-membrane interaction. There are very few studies on changes across the dialyser. Hence, it was planned to study the immediate changes that occur due to passage of blood through the dialyser. Changes between the arterial and venous ends of the dialyser after 1h of dialysis were studied in four combinations of dialysate and membrane. There was a significant decrease in plasma vitamin E concentrations in all the groups during first-use dialysis. This was not observed with re-use dialysis. A decrease in plasma lipid peroxides was also observed in all the groups with both first and re-use dialysis. There was no significant difference in the parameters studied among the four types of dialysis. A less severe, reactive oxygen radical generation was observed with re-use of membranes.
Biochemical analysis of pleural fluid: what should we measure?
Authors: Tarn Anne C , Lapworth Ruth
Published: October 2002

Biochemical examination of pleural fluid is usually done to try to identify the cause of a pleural effusion. The various analytes that have been suggested for this are reviewed and evaluated.

Distinguishing whether the effusion is an exudate or transudate is a pragmatic first step, with further investigations dictated by the clinical features and these results. Total protein and lactate dehydrogenase were used first; Light's criteria were published in 1972 and since then additional markers including cholesterol, bilirubin and albumin gradient plus combinations of these have been proposed. Although combination testing does improve the sensitivity for diagnosis of an exudate, this is at the expense of specificity. Measurement of fluid to serum ratios appears to confer no advantage, and if a single test is required total protein performs as well as any.

Additional tests may be useful in specific circumstances: pleural fluid pH may aid decisions over drainage of a parapneumonic effusion; glucose may indicate an effusion associated with rheumatoid arthritis; and adenosine deaminase may help with the diagnosis of tuberculous effusions.
Relationships between serum (ZZ)-bilirubin, its subfractions and biliverdin concentrations in infants at 1-month check-ups
Authors: Itoh Susumu , Kondo Masatoshi , Imai Tadashi , Kusaka Takashi , Isobe Kenichi , Onishi Shoju
Published: October 2002

In 150 infants, including those with breast milk jaundice, who were brought to our hospital for their 1-month check-ups, the serum concentrations of (ZZ)-bilirubin, its subfractions and biliverdin were measured by high-performance liquid chromatography and the relationships among them investigated. (ZZ)Bilirubin was found to have the highest serum concentration, followed by (ZE)bilirubin, accounting for 14·0 (geometric mean) % of (ZZ)-bilirubin. Biliverdin had a serum concentration of 0·95% of (ZZ)-bilirubin. There was only a small amount of total (di- and mono-) glucuronosyl bilirubin, 0·42% of (ZZ)-bilirubin. (ZE)Bilirubin, (EZ)-bilirubin, (EZ)-cyclobilirubin, biliverdin, diglucuronosyl bilirubin and monoglucuronosyl bilirubin (C-8 and C-12) showed positive logarithmic correlations with (ZZ)-bilirubin ( R2=0·16 or above, P <0·05). (ZE)-Bilirubin showed a significant positive logarithmic correlation with (ZZ)-bilirubin ( R2=0·863, P <0·0001). Furthermore, (EZ)-cyclobilirubin, the most important photoisomer in phototherapy for neonatal hyperbilirubinaemia, was detected in very small amounts in approximately half of the neonates (84 of 150) when they were in conditions of only weak ambient light. The relationship between total glucuronosyl bilirubin and (ZZ)-bilirubin concentrations fitted a model of saturation kinetics of bilirubin UDP-glucuronosyltransferase.
Reference intervals for thyroid hormones in pregnant Chinese women
Authors: Panesar N S , Li C Y , Rogers M S
Published: October 2002

Objective: To establish gestation-related reference intervals for thyroid hormones in a Chinese population.

Materials and methods: A prospective study with 343 healthy pregnant women (5-41 weeks) and 63 non-pregnant controls. Thyroid stimulating hormone (TSH), free thyroxine (T4) and tri-iodothyronine (T3) (and human chorionic gonadotrophin) were measured by immunoassays. The median, 2·5th and 97·5th percentiles at 4-week intervals werecalculated. Data were also analysedfor significant trends using ANOVA.

Results: Free T3 decreased during pregnancy, whereas free T4 initially increased, peaking between 9-13 weeks and then decreased, the decline becoming significant by week 21. TSH mirrored changes in free T4. Conclusion : The gestation-related reference intervals for thyroid hormones should alleviate the misinterpretation of thyroid function in pregnancy.
Measurement of pancreatic lipase activity in serum by a kinetic colorimetric assay using a new chromogenic substrate
Authors: Panteghini Mauro , Bonora Roberto , Pagani Franca
Published: October 2002

We evaluate a new assay reagent for lipase determination, based on the use of 1,2- o-dilauryl- rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) as substrate. DGGR is cleaved by lipase, resulting in an unstable dicarbonic acid ester which is spontaneously hydrolysed to yield glutaric acid and methylresorufin, a bluish-purple chromophore with peak absorption at 580nm. The rate of methylresorufin formation is directly proportional to the lipase activity in the sample. Bile salts, colipase and calcium chloride are included to provide optimal reactivity and specificity. Analysis of total imprecision gave a coefficient of variation of between 5·7% and 9·6%. Anticoagulants, common interfering substances and carboxylesterase had no effect on the assay, but interference by increased concentrations of serum triglycerides was noted. Good correlations were obtained with turbidimetry and a coupled enzymatic method. The estimated reference interval was 6-38U/L. The unique characteristics of the chromogenic substrate qualify the present method as an innovative approach to serum lipase analysis.
Performance of a novel spectrophotometric lithium assay on a routine biochemistry analyser
Authors: Rumbelow B , Peake M
Published: October 2002

A new spectrophotometric lithium assay was assessed after adaption to a Hitachi 917. Results on this analyser were in close agreement with lithium measured on a flame photometer (95% confidence interval ± 0·06 mmol/L, n = 120). Assay precision was < 2·5% over a range of lithium concentrations from 0·5- 3·0 mmol/L. The assay was linear to 3 mmol/L and interference from haemolysis, icterus, lipaemia and other metal ions was minimal. The assay is a useful substitute or "back-up" for traditional lithium assays. Improved "on-board" calibration stability (currently 24 h) is required by improving the stability of uncapped reagent.
Evaluation of specific high-performance liquid-chromatographic determinations of urinary metanephrine and normetanephrine by comparison with isotope dilution mass spectrometry
Authors: Willemsen Jacques J , Ross H Alec , Wolthers Bert G , Sweep C G J Fred , Kema Ido P
Published: October 2002

A method for the determination of metanephrine (MN; also known as metadrenaline), normetanephrine (NMN; also known as normetadrenaline) and 3- methoxytyramine (3-MT) in human urine using high-performance liquid chromatography followed by electrochemical detection (ECD) was validated primarily by comparing the results with those obtained by a gas chromatography-mass spectrometry (GC-MS) reference method. Correlation coefficients of 0.93, 0.94 and 0.91 were obtained for MN, NMN and 3-MT, respectively, in a group of healthy controls consisting of 30 women and 30 men. A systematic difference was detected only for 3-MT (- 16%). Further tests of accuracy (linearity and recovery) and precision demonstrated that the described method must be considered to be a reliable approach to assess urinary metanephrines in the diagnosis of phaeochromocytoma. At lower concentrations (MN, 248 nmol/L; NMN, 434 nmol/L; 3-MT, 402 nmol/L), within-assay coefficients of variation were close to 5% or less (5·3, 4·6 and 2·2%, respectively) and between-assay coefficients of variation were 8·9, 11·2 and 12·3%, respectively, for the same low levels. This raises the possibility that this method can also be applied to assess urinary free, unconjugated metanephrines. Sex differences were detected for MN and NMN excretion when expressed in nmol per 24 h and nmol/mmol creatinine, respectively, by both ECD and GC-MS methods.
Biochemical detection and monitoring of alcohol abuse and abstinence
Authors: Sharpe Peter C
Published: October 2002

The merits and limitations of traditional and new markers for alcohol abuse (and abstinence) are critically examined for detection and monitoring of alcoholics, hazardous drinkers and binge drinkers. The traditional markers discussed include γ-glutamyltransferase (GGT), aspartate and alanine aminotransaminases (AST, ALT) and mean corpuscular volume (MCV); new markers include mitochondrial AST, carbohydrate-deficient transferrin (CDT), serum/urine 5- hydroxytryptophol, β-hexosaminidase and acetaldehyde adducts. The strengths and weaknesses of several of the self-reporting screening questionnaires are also explored. No laboratory test is reliable enough on its own to support a diagnosis of alcoholism. Sensitivities and specificities vary considerably and depend on the population concerned. GGT continues to remain the test that combines greatest convenience and sensitivity; its diagnostic accuracy can be enhanced by combination with other traditional markers (AST, ALT, MCV). None of the newer markers offers significant advantage, although CDT seems to be better at monitoring patients for increased alcohol consumption or progress towards abstinence.
Artefactual reduction in plasma total carbon dioxide concentration in children
Authors: Williams Andrew J , Norris Lisa , Coakley John C
Published: October 2002

Methods The effect on plasma total carbon dioxide (ctCO2) of collecting a small volume of blood into a large tube was investigated. In a 7-month-old infant presenting with diarrhoea the initial ctCO2 was low when 0·3 mL of sample was received in a 4-mL tube. To investigate this further blood samples were obtained from three volunteers on five occasions and various volumes were placed in a 4 mL container and analysed after varying intervals. Results When the sample volume was less than 2 mL there was a significant decrease in ctCO2. A 42% decrease was seen in the tube containing 0·3 mL after 4 h. Conclusions We recommend that when a small volume of sample is collected it should be placed in a smaller tube with minimal air space.
Effect of low protein concentration on serum sodium measurement: pseudohypernatraemia and pseudonormonatraemia!
Authors: Lang T , Prinsloo P , Broughton A. F. , Lawson N , Marenah C. B.
Published: October 2002

Background The effect of high concentrations of protein or lipid on the measurement of plasma sodium by indirect ion selective electrode (ISE) causing pseudohyponatraemia and pseudonormonatraemia is well described. The effect of a low total protein concentration, however, has not been described. Methods In order to examine this, over a 2-week period the total protein concentration was measured on all samples received for urea and electrolyte measurement. All samples with a low (< 50 g/L) or a high (> 80 g/L) total protein concentration had sodium measured by both direct and indirect ISE. Results There were approximately equal numbers of samples with a protein concentration less than 50 g/L (1·3%) as samples with a protein concentration greater than 80 g/L (1·3%). The frequency of erroneous sodium results owing to the use of an indirect ISE was less in hypoproteinaemic (2%) than in hyperproteinaemic (20%) samples.
Correlation between serum magnesium and blood cyclosporine A concentrations in renal transplant recipients
Authors: Thakur V , Kumar R , Dhawan I. K.
Published: October 2002

Background Low total serum magnesium concentration has been reported in renal transplant recipients on cyclosporine therapy, and this is a risk factor for hypertension and cardiac death. No study is yet available from the Indian subcontinent on the relationship between total serum magnesium and cyclosporine A concentration. Methods Blood cyclosporine A and total serum magnesium concentrations were estimated in 31 post renal transplant patients. Sixteen chronic renal failure patients who had not yet received a transplant served as controls. Results The mean total serum magnesium in post-transplant patients was 0·64± 0·11 mmol/L ( n = 31), which was significantly lower ( P < 0·001) than in the controls (1·0± 0·16 mmol/L). An inverse correlation was found between total serum magnesium and blood cyclosporine A concentration ( r = -0·532). Systolic and diastolic blood pressures were also higher in the cyclosporine-treated patients. Conclusions We conclude that serum magnesium should be monitored regularly in patients receiving cyclosporine A.
Novel nephelometric assay for measurement of complement 3d
Authors: Bossuyt Xavier , Sneyers Lutgarde , Mariën Godelieve , Vranken Guido
Published: October 2002

Background This report describes a nephelometric assay for measuring complement 3d (C3d). Methods C3d was separated from C3 and the other C3 split products by polyethylene glycol precipitation. The supernatant containing C3d was then measured by rate nephelometry in a Beckman Immage rate nephelometer using a specific antibody. Calibration was performed with dilutions of a standard, which was obtained by incubating a serum pool at 37°C for 7 days. This incubation step allowed the activation and breakdown of C3 into C3d. Results The assay was linear across the normal and pathological range. Precision studies showed within-run and between-run coefficients of variation of < 5% and < 6%, respectively. The nephelometric results are comparable with those obtained by radial immunodiffusion. Neither haemoglobin nor lipids interfere with the assay.
Limited clinical utility of high-sensitivity plasma C-reactive protein assays
Authors: Campbell Bruce , Badrick Tony , Flatman Robert , Kanowski David
Published: October 2002

Many recent studies have shown a relationship between plasma C-reactive protein (CRP) concentrations and risk of cardiovascular disease. However, the intra-individual variation in plasma CRP concentrations is large. Use of plasma CRP measurement in individual patients is likely to result in many being misclassified in their risk status. Use of repeated measurements is not a practical solution to this problem.
Naturally occurring mutation, Asp70His, in human butyrylcholinesterase
Authors: Boeck Andreea Ticu , Fry Debra L , Sastre Antonio , Lockridge Oksana
Published: October 2002

Background: People with genetic variants of butyrylcholinesterase can have hours of prolonged apnoea after a normal dose of succinylcholine or mivacurium. Methods Serum samples from 308 persons living in mid-USA were phenotyped to identify the atypical and fluoride variants. 308 samples were analysed for the K variant by DNA amplification, digestion with Mae III and gel electrophoresis. Amplified DNA from 16 samples was sequenced to identify the D70G, T243M and D70H mutations. Values for kcat and Km were determined for the D70H mutant BChE expressed in 293T cells. Results: A new mutation, Asp70His, was identified. This mutation is located in the peripheral anionic site of butyrylcholinesterase, where it causes a 10-fold decrease in binding affinity for positively charged substrates. Conclusion: People homozygous for the Asp70His mutation are expected to have prolonged apnoea in response to succinylcholine or mivacurium, similar to people with the Asp70Gly mutation.
Falsely increased prostate-specific antigen concentration attributed to heterophilic antibodies
Authors: Camacho Tomás , Mora Josefina , Segura Ana , Guitián Javier , Lema Fernando , Bandín Jesús , Rodríguez-Espinosa José
Published: October 2002

We describe a 50-year-old man with a serum total prostatic-specific antigen concentration of 67.6 µg/L (reference range 0-4 µg/L) revealed as part of an annual health check programme. Clinical examination failed to identify any prostatic abnormality, and laboratory investigation indicated positive interference due to heterophilic antibodies.
Role of bile acid measurement in pregnancy
Authors: Walker Ian AL , Nelson-Piercy Catherine , Williamson Catherine
Published: October 2002

The diagnosis of obstetric cholestasis (OC) has serious implications for maternal, and especially fetal, health. Total serum bile acid concentration is an important investigation in any woman with itching in the absence of a rash during pregnancy. Results should be available within 1-2 working days. Pruritus plus raised total bile acids in the third trimester suggests a diagnosis of OC. Other biochemical abnormalities, usually a raised alanine aminotransferase, accompany or follow the finding of raised bile acids. Bile acids are sensitive, but not specific, markers for OC. The diagnosis is one of exclusion. The clinician should remain alert to other causes of liver dysfunction, either specific to pregnancy or not. Effective treatment is available that improves maternal biochemical indices and well-being. It is not clear whether such treatment reduces the risks to the fetus. More active management of OC pregnancies has reduced the associated fetal and perinatal mortality.
Review of a pilot quality-assessment program for interpretative comments
Authors: Vasikaran SD , Penberthy L , Gill J , Scott S , Sikaris KA
Published: October 2002

Background Interpretative commenting constitutes an important aspect of the post-analytical phase in chemical pathology, but has only recently been the subject of quality assessment. The Royal College of Pathologists of Australasia (RCPA)-Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program is currently in its third year, having started in 2000 as a pilot program. We present a review of the pilot program. Methods The program is aimed at individuals rather than laboratories. Two cases were circulated to participants of the Chemical Pathology Quality Assurance Program every month over a 6-month period. The case report contained the age and sex of the patient, together with brief clinical notes, the biochemistry results for commenting and other information of relevance. Three lines of space were given for the comment. The comments received from participants were broken down into their components and translated into common key phrases for the purpose of summarization and analysis. A histogram of the frequency of use of the common key phrases was generated. The comments or the key phrases were not given scores or marks, nor was any other indication given as to the appropriateness of their comments. Results This approach of simple peer-group comparison of comments without any assessment of the appropriateness of the comments was found to be inadequate; thus, when the program continues, key phrases will be classified according to degree of appropriateness and a suggested comment for each case will be proposed by an 'expert' panel. Conclusions The program can serve a useful role in continuing education. Clinical biochemists and trainees who add interpretative comments to results produced by their laboratory, or give interpretative advice over the telephone, may potentially benefit from participating in this program.
Effects of contamination of blood specimens with liquid potassium-EDTA anticoagulant
Authors: Davidson D Fraser
Published: October 2002

Background Use of the anticoagulant EDTA, in high-concentration liquid form, in blood collection tubes can lead to cross-contamination of routine biochemistry specimens. Methods In the present study, tests affected by EDTA in the sample were potassium, calcium, magnesium, unsaturated iron-binding capacity, bicarbonate, aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine kinase, alkaline phosphatase and amylase. The likely mechanisms are discussed. Conclusions In the interests of best practice, the identification of subtle contamination of blood specimens for biochemical analysis requires a sensitive method for measurement of EDTA itself.
Application of polymerase chain reaction with oligoligation assay to determine genotype in individuals presenting with congenital adrenal hyperplasia
Authors: Hogg Janet E , Gaffney Dairena , Hector Ralph D , Coleman Michelle M , Wallace AM
Published: October 2002

Background Current methods for the molecular diagnosis of the 21-hydroxylase deficiency variant of congenital adrenal hyperplasia use cumbersome combinations of Southern blotting and polymerase chain reaction (PCR). The aim of the present study was to develop a practical genetic test for the unambiguous diagnosis of this condition, and to use this procedure to determine the range of mutations in Scottish patients. In addition, we wished to obtain further information to that currently available in the literature regarding the correlation of genotype with phenotype in any identified carriers. Methods We studied five Scottish probands and their family members. To try to obviate the need for Southern blotting, we investigated a technique that uses the oligoligation chain reaction after gene-specific PCR. Results We found a spectrum of mutations in the ten unrelated mutant alleles studied. These consisted of at least three different 30-kb deletions, two intron 2 splice-site mutations and single occurrences of the I172N, V281L and R356W substitutions. Conclusions The genotype-phenotype correlations agreed with those previously described. In addition, our results suggest that there is no predominant Scottish genotype.
Serum concentration of cystatin C is not affected by cellular proliferation in patients with proliferative haematological disorders
Authors: Mojiminiyi OA , Marouf R , Abdella N , Kortom M , Abdul-Razzak R
Published: October 2002

Background Recent reports have shown elevated concentrations of serum cystatin C (CC) in patients with solid tumours. The aim of our study was to investigate whether patients with proliferative haematological disorders have increased serum concentrations of CC compared with normal subjects. Methods Full blood count, serum CC, β2-microglobulin (β2M) and serum creatinine were determined in 27 apparently healthy subjects and 35 patients with proliferative haematological disorders. Creatinine clearance was calculated using the Cockroft-Gault formula. Results CC and β2M showed a significant correlation with each other ( r = 0·96, P < 0·0001). Serum β2M ( P = 0·001) and the serum β2M:CC ratio ( P = 0·001) were significantly higher in the patients with normal renal function than in controls, but serum CC was not significantly different ( P = 0·08). CC did not show a significant correlation with blood count parameters. Discussion Compared with β2M and the β2M:CC ratio, serum CC is not influenced by cell proliferation in haematological disorders.
Cross-reaction of human chorionic gonadotrophin in Immulite 2000 luteinizing hormone assay
Authors: Vivekanandan S , Andrew Charles E
Published: October 2002

Background and method The cross-reactivity of human chorionic gonadotrophin (hCG) in the new DPC Immulite 2000 luteinizing hormone immunoassay was studied using sera from healthy pregnant women and pooled serum spiked with hCG standard IRP 75/537. Results and Conclusion Significant positive bias was seen in sera from pregnant women and in IRP 75/537 spiked serum.
Hormone replacement therapy (oestradiol-only preparations): can the laboratory recommend a concentration of plasma oestradiol to protect against osteoporosis?
Authors: Armston Annie , Wood Peter
Published: October 2002

Target concentrations of plasma oestradiol to protect against osteoporosis have now been published in at least one textbook1 and are increasingly discussed by clinicians. A survey of the literature revealed that many reports do not give details of oestradiol assay methods, despite the fact that there is a wide range of biases. Plasma oestradiol measurements made after ingestion of equine oestrogen preparations are not valid, and for oral oestradiol and oestradiol valerate preparations a single untimed sample does not give a reliable estimate of the average exposure over 24 h. Oestradiol measurements in plasma from women using patch, gel or implant preparations could be useful provided that consideration is given to the time of sampling and to the assay method used, although target levels have not been established. Further studies are required in this area.
Decision limit for troponin I and assay performance
Authors: Sheehan Paul , Blennerhassett John , Vasikaran Samuel D
Published: October 2002

Background The redefinition of acute myocardial infarction by the Joint European Society of Cardiology and American College of Cardiology places troponin at the centre of the diagnostic strategy, in addition to lowering the diagnostic cut-off to the 99th centile of a healthy reference population. The required percentage coefficient of variation (%CV) for the assay at this level is 10. Recent publications have examined the utility of the Bayer ACS:180 troponin I assay at a cut-off of 0·1 μg/L to risk-stratify patients with non-ST-elevation myocardial infarction. Methods This study examines the appropriateness of using this assay at this cut-off in individual patients. It also examines the functional sensitivity of the assay and assesses the impact of sample quality on assay performance. Results At the decision limit of 0·1 μg/L, 8% of patients would be assigned to a different risk group on repeat analysis of the same sample on the ACS:180 due to assay imprecision. The functional sensitivity (at inter-assay %CV = 10) of the ACS:180 troponin I assay was determined to be 0·27 μg/L. Nineteen of 4850 routine samples (0·39%) failed duplicate precision checks as a result of poor sample quality; this was usually due to the presence of small fibrin particles. Conclusions Careful attention to sample quality is vital in troponin I measurement. The use of the Bayer assay for risk stratification at a cut-off of 0·1 μg/L can lead to inconsistency of risk assessment in a small but significant proportion of cases.
Mitochondrial dysfunction and the role of the non-specialist laboratory
Authors: Hancock Maggie R
Published: October 2002

Each human cell contains at least 1000 mitochondria, each containing several copies of mitochondrial DNA. This DNA is tiny compared with the nuclear genome, and its structure and products have been fully elucidated. Whilst oxidative phosphorylation depends on the polypeptides encoded by mitochondrial DNA, it also requires a huge number of nuclear DNA products. Inherited deleterious mutations of mitochondrial DNA leading to inefficient oxidative phosphorylation have been described as 'mitochondrial disorders', with a variety of clinical presentations. When similar clinical presentations occur with no discernible mutation of mitochondrial DNA, histological and biochemical evidence is required for diagnosis. The number of these laboratory-proven inherited mitochondrial disorders is growing. It is also becoming clear that mitochondrial DNA defects can be acquired, the most common cause being therapy with highly active antiretroviral therapy (HAART) for human immunodeficiency virus-1 (HIV-1) infection. Whilst definitive diagnosis of inherited or acquired mitochrondrial dysfunction requires access to specialist laboratory techniques, routine laboratories have a role to play in the initial investigation and monitoring of these conditions.
Solid-phase extraction in clinical biochemistry
Authors: Walker Valerie , Mills Graham A
Published: October 2002

In order to measure low concentrations of analytes in plasma and urine, it is often necessary to extract and concentrate them. With solid-phase extraction (SPE), this is achieved by partitioning the analytes between a solid and a liquid or headspace vapour. A wide range of high-quality materials is now available to do this, offering a variety of separation modes for different applications. These include partitioning using reversed-phase, normal-phase, ion-exchange, restricted-access and immunoaffinity sorbents or molecularly imprinted polymers and, increasingly, combinations of these processes. Solid-phase microextraction was introduced to analyse volatile and semi-volatile compounds. The range of sampling formats has expanded from simple packed syringes to cartridges, disks, SPE pipette tips and 96-well plates. These developments have facilitated automated off- and on-line sample processing. The basic principles of SPE and the recent innovations are reviewed here. This is a technological growth area. Some of the developments are finding application in clinical toxicology. However, they could also be of wider value in clinical chemistry - for example, for analyses of volatile and non-volatile metabolites, peptides, radioactive elements and trace metal speciation.
Association between HaeIII polymorphism of scavenger receptor class B type I gene and plasma HDL-cholesterol concentration
Authors: Hong Seung Ho , Kim Young-Ree , Yoon Yeo Min , Min Won Ki , Chun Sa Il , Kim Jin Q
Published: October 2002

Background: Evidence has recently been found for significant associations between genetic variation within the scavenger receptor class B type I gene ( SR-BI), plasma lipids and anthropometric measurements in healthy Caucasians. The present case-control study was conducted to determine whether there is an association between three polymorphisms identified by the restriction endonucleases HaeIII, AluI and ApaI of SR-BI and coronary artery disease (CAD) in Korean subjects.

Methods: DNA was extracted from 137 subjects with CAD and 124 age-matched controls; it was amplified using the polymerase chain reaction. Individual alleles at each of the three polymorphic sites were identified by digestion with the appropriate restriction enzyme.

Results: Only a single allele was identified at the AluI and ApaI polymorphic sites. The frequency of the common (+) allele at the HaeIII polymorphic site was higher in CAD patients than in the controls ( P = 0·001). The concentrations of plasma HDL-cholesterol and apolipoprotein AI also varied significantly among HaeIII genotypes in the CAD patients. The common (+) allele of the HaeIII polymorphism was associated with a lower body mass index in female controls.

Conclusions: Allele frequencies of the AluI and ApaI polymorphisms in this study were different to those in a Caucasian population studied previously, suggesting a difference in the genetic background. Further comparative studies of SR-BI polymorphism in other racial or ethnic groups should therefore prove to be of value.
γ Heavy chain disease screening showing a discrepancy between electrophoretic and nephelometric determinations of serum γ globulin concentration
Authors: Takatani Tsunenori , Morita Keiko , Takaoka Naomi , Tatsumi Masatsuga , Okuno Yorio , Masutani Takayuki , Murakawa Koichi , Fukui Akihiro , Tsukaguchi Nobuhiko , Okamoto Yasuyuki
Published: October 2002

A 75-year-old woman with rheumatoid arthritis showed a discrepancy between the reduced level of serum γ globulin on cellulose acetate electrophoresis and the normal level of serum IgG determined by laser nephelometry. Although no M-peak was detectable on cellulose acetate electrophoresis, immunoelectrophoresis of the patient's serum revealed a monoclonal protein reacting with anti-IgG antiserum but not with anti-κ or anti-λ light chain antiserum. Western blotting of the patient's serum showed abnormal low-molecular-weight γ chains. Thus, the patient was diagnosed with γ heavy chain disease. A comparison of γ globulin levels determined by different methods may be useful when screening for this disease.
Analysis of carbon monoxide
Authors: Widdop Brian
Published: October 2002

The degree of exposure to carbon monoxide is most often assessed by measuring the blood carboxyhaemoglobin saturation. This measurement is relevant to investigations of acute accidental or deliberate poisoning and of chronic exposure in a domestic or work place environment. Simple spectrophotometric methods based on differential protein precipitation or dithionite reduction are prone to interference from other haemoglobin pigments and are imprecise for low-level estimations. Automated spectrophotometric devices (CO-oximeters) that estimate simultaneously total haemoglobin, percentage oxyhaemoglobin and percentage carboxyhaemoglobin have acceptable accuracy for carboxyhaemoglobin saturation levels of > 5% and are recommended for most clinical purposes. For the investigation of low-level exposure and the detection of increased haemolysis in neonates, more sensitive methods involving the release of carbon monoxide and its measurement by gas chromatography are required. Gas chromatographic methods are also appropriate when examining post-mortem blood samples where putrefaction or heat stress has resulted in a significant change in haemoglobin composition.
Biochemical detection of minor myocardial injury after elective, uncomplicated, successful percutaneous coronary intervention in patients with stable angina: clinical outcome
Authors: Saadeddin Salam M , Habbab Moh'd A , Sobki Samia H , Ferns Gordon A
Published: October 2002

Background: Minor elevations of creatine kinase MB isoform (CK-MB) identified a population with a worse long-term prognosis after successful coronary intervention. Recent studies provide evidence that cardiac troponin I (cTnI) is more sensitive than CK-MB for the detection of minor myocardial injury after coronary intervention. The purpose of the study was to determine the prognostic value of cTnI elevation after elective uncomplicated successful percutaneous coronary intervention (PCI).

Methods: cTnI was measured in 96 patients with stable angina before and 24 h after elective uncomplicated successful percutaneous transluminal coronary angioplasty (PTCA) with or without stenting. Patients were followed up for adverse cardiac events (recurrent angina, non-fatal myocardial infarction, cardiac death, repeat PCI or coronary bypass surgery). Procedure success was achieved in all cases.

Results: Cardiac events were best predicted by cTnI when a cut-off value of 2·0 μg/L was used. Abnormal cTnI values at 24 h after PCI were observed in 26 patients (27%). Over a follow-up period of 24 months with no significant difference in the medication used, the incidence of recurrent angina, repeat PCI, coronary bypass surgery and cardiac death was 54%, 46%, 4% and 4%, respectively, in the cTnI-positive patients versus 27%, 16%, 4% and 0% in the cTnI-negative patients. Kaplan-Meier survival analysis showed that cTnI elevation was a significant correlate of cardiac events ( P = 0·0198, by log rank analysis).

Conclusions: Elevation of cTnI is not uncommon after elective uncomplicated successful PCI in patients with stable angina and this elevation might be a marker of adverse long-term outcome.
Evaluation of a sandwich enzyme-linked immunosorbent assay for the measurement of serum heart fatty acid-binding protein
Authors: Pagani Franca , Bonora Roberto , Bonetti Graziella , Panteghini Mauro
Published: October 2002

Background: We evaluated the sandwich enzyme-linked immunosorbent assay (ELISA) MARKIT®-M for the determination of heart fatty-acid-binding protein (H-FABP).

Results and Conclusions: The between-run coefficient of variation of this assay was <3·9 and it showed good correlation with a previously established ELISA method. The upper reference limit in 30 healthy individuals was 6·1 μg/L. Admission serum H-FABP was evaluated against myoglobin in 41 patients with suspected myocardial infarction (onset of symptoms ≤ 5 h). H-FABP showed the same diagnostic efficiency as myoglobin [area (standard error) under the receiver operating characteristic curve: 0·798 (0·079) for H-FABP, 0·771 (0·085) for myoglobin, P = 0·55]. However, using the upper reference limit as decision cut-off, the sensitivity for H-FABP [91%; 95% confidence interval (CI): 76-98%] was significantly ( P = 0·019) higher than that of myoglobin (65%; 95% CI: 47-80%).
Severe hypertriglyceridaemia associated with human immunodeficiency virus and highly active antiretroviral therapy
Authors: Carling RS , Hextall R , DeSilva PA , Barth JH
Published: October 2002

We report two cases of severe hypertriglyceridaemia associated with human immunodeficiency virus infection and highly active antiretroviral therapy (HAART). The first patient, a 39-year-old man, developed moderate hypertriglyceridaemia (5·88 mmol/L) and hypercholesterolaemia (7·0 mmol/L) after 8 months of HAART. When his therapy was altered, triglyceride and cholesterol concentrations increased further to 15·9 and 10·9 mmol/L, respectively, after 6 weeks. The second patient, a 31-year-old man, presented with triglyceride and cholesterol concentrations of 16·2 and 5·7 mmol/L, respectively, following an 8-year history of HAART. Therapy was changed, but 1 month later the triglyceride concentration had increased to 39·4 mmol/L and the cholesterol concentration to 12·1 mmol/L. Both patients were managed by a change in HAART and the introduction of a fibric acid derivative. Although neither patient displayed any clinical symptoms associated with hypertriglyceridaemia, it is important to recognize such cases because of the associated risk of pancreatitis and coronary disease.
Are there any clinical indications for measuring IgG subclasses?
Authors: Maguire GA , Kumararatne DS , Joyce HJ
Published: October 2002

It is questionable as to whether a low serum concentration of one of the IgG subclasses identifies a disease state. A low IgG1 concentration is found in primary or secondary immunodeficiency states but does not occur in isolation. Low IgG2 concentration is associated with an increased risk of bacterial infections but only in some individuals and not in others. Isolated IgG3 and IgG4 deficiency have not been convincingly demonstrated. Therefore, the isolated finding of low concentrations of one or more IgG subclass does not identify individuals at risk. In contrast, the finding of low serum concentrations of antibodies to specific bacterial antigens ( Haemophilus influenzae type B, pneumococcus, tetanus and diphtheria) does identify individuals at risk and these measurements should be used in preference to IgG subclass measurement.
Labyrinthine involvement and multiple perforations of the tympanic membrane in acute otitis media due to group A streptococci
Authors: Kanazawa Takeharu , Hagiwara Hideo , Kitamura Ken
Published: October 2002

We present here three cases of acute otitis media caused by a virulent group A streptococcal infection that rapidly led to deterioration in hearing. Two of the three cases presented with severe sensorineural and mixed hearing loss with multiple tympanic membrane perforations, and the third presented with severe bilateral sensorineural hearing loss following acute otitis media involving group A streptococci. All patients were treated with systemic (piperacillin) and topical antibiotics (ofloxacin ear drops): one patient also received a systemic steroid (betamethasone). Deafness persisted in one patient but in the other two, hearing gradually recovered. Severe cytotoxicity was considered to have occurred in all patients, resulting in multiple perforations of the tympanic membrane and necrosis in the middle ear.
Submandibular salivary duct cyst mimicking an external laryngocele
Authors: Back G. W. , Fahmy F. , Hosni A.
Published: October 2002

The clinical and radiological differential diagnosis of cystic lesions of the submandibular region can be difficult. We report an unusual case of a submandibular salivary duct cyst mimicking an external laryngocele on presentation by appearing to expand on Valsalva manoeuvre, and where computed tomography (CT) scanning was unhelpful in reaching a diagnosis. We present the case, discuss the theories of pathogenesis, and review the literature on the differential diagnosis of cystic lesions in the submandibular region.
Optimum imaging for sinonasal malignancy
Authors: Lloyd Glyn , Lund Valerie J. , Howard David , Savy Lloyd
Published: October 2002

A combination of computed tomography (CT) and magnetic resonance imaging (MRI) is now established as the optimum assessment of sinonasal malignancy. CT and MRI are of particular value in assessing the skull base, orbit and pteryo-palatine and infratemporal fossae. Although MRI offers better differentiation of tumour from surrounding tissue and fluid, coronal CT is still required for the demonstration of bone erosion particularly in the region of the cribriform plate. Thus the extent of local tumour spread may be determined with a degree of accuracy in excess of 98 per cent. However, the final determinant of penetration of the dura and orbital periosteum requires per-operative frozen section assessment. A knowledge of the tissue characteristics and site of origin can be of value in distinguishing some of the commoner sinonasal malignancies such as squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, olfactory neuroblastoma and chondrosarcoma. Imaging, particularly MRI also plays an important role in the post-therapeutic follow-up of patients, indicating areas of residual or recurrent disease, defining suspicious areas for biopsy. Post-operative surveillance is best achieved with three planar T1-weighted MRI, with, and without, gadolinium and axial T2-weighted sequences. The subtraction of the T1 pre- and post gadolinium T1 sequences can be of particular value in delineating recurrence.
Ear witness
Authors: Feenstra L. , van der Lugt C.
Published: October 2002

A description is given of some aspects of the normal human auricle. The physiognomy of the auricle is different for every individual which leads to the possibility of identifying people based on their auricles. Indeed this has even led to the reading of earprints similar to fingerprints, a fact not generally known amongst ENT-specialists. This highly specialized knowledge has been developed within a special branch of forensic medicine and criminology, called ‘earology’ or ‘otomorphology’. Two illustrative case histories are presented.
Post-cricoid web associated with Rubinstein-Taybi syndrome
Authors: Scott A. R. , Proops D. W. , Kunick T.K.
Published: October 2002

A case of dysphagia due to a post-cricoid web in a seven-year-old boy with Rubinstein-Taybi syndrome is presented. the main features of this syndrome are summarized with particular reference to dysphagia and with previous cases of post-cricoid webs in children reviewed.
Vestibular schwannoma presenting as sudden deafness
Authors: Inoue Y. , Kanzaki J. , Ogawa K.
Published: October 2002

In this study, we analysed the clinical and audiological features of 24 vestibular schwannoma patients presenting with sudden deafness who visited our hospital within 10 days after its onset. The relationships between the prognosis of hearing loss and the clinical and audiological features including the pure-tone average (PTA), the presence of dizziness and/or vertigo, the tumour size and the auditory brain stem response (ABR) findings were evaluated. Hearing recovery depended on the PTA and tumour size, but even a small tumour induced sudden deafness. Impaired hearing completely recovered in five our of 24 patients. ABR findings indicated that the aetiology of sudden deafness in the vestibular schwannoma patients might vary in each patient.
Manual dexterity and successful hearing aid use
Authors: Kumar Manoj , Hickey Simon , Shaw Steve
Published: October 2002

Fine dexterity of the hand might be expected to correlate with the successful use of a hearing aid. In this study, the manual dexterity of 30 individuals between 65 and 85 years using a hearing aid was tested by the Purdue pegboard test and the result was compared to the benefit obtained from the use of a hearing aid assessed by a questionnaire. Of the 30 individuals included in this study 16 were wearing a ’behind the ear’ type of hearing aid and the rest had an ’in the ear’ type of hearing aid. A comparison is made between the two types of heariing aids. The results demonstrate a correlation between manual dexterity and successful use of a hearing aid when all the 30 individuals were considered as a single group. However, no such correlation was found for ’in the ear’ group when they were analysed separately.
Wegener’s granulomatosis: diagnostic dilemma
Authors: Banerjee A. , Armas J. M. , Dempster J. H.
Published: October 2002

Wegener’s granulomatosis is a systemic disease characterized by a granulomatous lesion that can affect any organ throughout the body.

This case-report illustrates the problem posed by a patient presenting with bilateral serous otitis media with marked sensorineural hearing loss, facial nerve paralysis and an atypical serological picture. The importance of early diagnosis and the protocol for the management of a patient with an uncertain diagnosis is discussed. Due to atypical presentations, only a high index of suspicion will ensure an early diagnosis.
Meningioma in the internal auditory canal
Authors: Devesa P. Martinez , Wareing M. J. , Moffat D. A.
Published: October 2002

A case is presented of an entirely intracanalicular meningioma in a 48-year-old woman that was excised via a conventional translabyrinthine approach to the internal auditory canal (IAC). Pre-operative magnetic resonance imaging (MRI) suggested that the tumour was a vestibular schwannoma (VS). Histological examination confirmed the intra-operative impression that the tumour was a meningioma. Although VS is by far the commonest intracanalicular tumour, the differential diagnosis includes meningioma. MRI is unable to distinguish between these two entities when the tumour is located entirely in the internal auditory canal.