Description

Clinical Chemistry is the leading forum for peer-reviewed, original research on innovative practices in today s clinical laboratory. In addition to being the most cited journal in the field (over 18,000 citations in 2005), Clin Chem has the highest Impact Factor (7.717 in 2005) among journals of clinical chemistry, clinical (or anatomic) pathology, analytical chemistry, and the subspecialties, such as transfusion medicine, clinical microbiology. The journal issued monthly, publishes contributions, either experimental or theoretical, that concern basic materials or principles, analytical and molecular diagnostic techniques, instrumentation, data processing, statistical analyses of data, clinical investigations in which chemistry has played a major role, or laboratory animal studies of chemically oriented problems of human disease.

Publications in this journal

• Temperature-Tolerant COLD-PCR Eliminates Temperature Stringency and Enables Robust Mutation Enrichment.

  Authors: E Castellanos-Rizaldos, Pingfang Liu, Coren A Milbury, Minakshi Guha, Angela Brisci, Laura Cremonesi, Maurizio Ferrari, Harvey Mamon, G Mike Makrigiorgos

  Clinical chemistry.

  BACKGROUND:Low-level mutations in clinical tumor samples often reside below mutation detection limits, thus leading to false negatives that may impact clinical diagnosis and patient management.BACKGROUND:Low-level mutations in clinical tumor samples often reside below mutation detection limits, thus leading to false negatives that may impact clinical diagnosis and patient management. COLD-PCR (coamplification at lower denaturation temperature PCR) is a technology that magnifies unknown mutations during PCR, thus enabling downstream mutation detection. However, a practical difficulty in applying COLD-PCR has been the requirement for strict control of the denaturation temperature for a given sequence, to within ±0.3 °C. This requirement precludes simultaneous mutation enrichment in sequences of substantially different melting temperature (T(m)) and limits the technique to a single sequence at a time. We present a temperature-tolerant (TT) approach (TT-COLD-PCR) that reduces this obstacle.METHODS:We describe thermocycling programs featuring a gradual increase of the denaturation temperature during COLD-PCR are described. This approach enabled enrichment of mutations when the cycling achieves the appropriate critical denaturation temperature of each DNA amplicon that is being amplified. Validation was provided for KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) and TP53 (tumor protein p53) exons 6-9 by use of dilutions of mutated DNA, clinical cancer samples, and plasma-circulating DNA.RESULTS:A single thermocycling program with a denaturation-temperature window of 2.5-3.0 °C enriches mutations in all DNA amplicons simultaneously, despite their different T(m)s. Mutation enrichments of 6-9-fold were obtained with TT-full-COLD-PCR. Higher mutation enrichments were obtained for the other 2 forms of COLD-PCR, fast-COLD-PCR, and ice-COLD-PCR.CONCLUSIONS:Low-level mutations in diverse amplicons with different T(m)s can be mutation enriched via TT-COLD-PCR provided that their T(m)s fall within the denaturation-temperature window applied during amplification. This approach enables simultaneous enrichment of mutations in several amplicons and increases significantly the versatility of COLD-PCR.

• Enough Evidence to Treat? The American College of Obstetricians and Gynecologists Guidelines.

  Authors: Sean C Blackwell

  Clinical chemistry.

• Binding of Hepcidin to Plasma Proteins.

  Authors: Outi Itkonen, Ulf-Håkan Stenman, Jaakko Parkkinen, Rabah Soliymani, Marc Baumann, Esa Hämäläinen

  Clinical chemistry.

• Ionic Cross Talk Can Lead to Overestimation of 3-Methoxytyramine during Quantification of Metanephrines by Mass Spectrometry.

  Authors: Jolaine M Twentyman, Kendall W Cradic, Ravinder J Singh, Stefan K Grebe

  Clinical chemistry.

• Detection of Microdeletion 22q11.2 in a Fetus by Next-Generation Sequencing of Maternal Plasma.

  Authors: Taylor J Jensen, Zeljko Dzakula, Cosmin Deciu, Dirk van den Boom, Mathias Ehrich

  Clinical chemistry.

  BACKGROUND:Efforts have been undertaken recently to assess the fetal genome through analysis of circulating cell-free (ccf) fetal DNA obtained from maternal plasma. Sequencing analysis of such ccfBACKGROUND:Efforts have been undertaken recently to assess the fetal genome through analysis of circulating cell-free (ccf) fetal DNA obtained from maternal plasma. Sequencing analysis of such ccf DNA has been shown to enable accurate prenatal detection of fetal aneuploidies, including trisomies of chromosomes 21, 18, and 13. We sought to extend these analyses to examine subchromosomal copy number variants through the sequencing of ccf DNA. We examined a clinically relevant genomic region, chromosome 22q11.2, the location of a series of well-characterized deletion anomalies that cause 22q11.2 deletion syndrome.METHODS:We sequenced ccf DNA isolated from maternal plasma samples obtained from 2 patients with confirmed 22q11.2 deletion syndrome and from 14 women at low risk for fetal chromosomal abnormalities. The latter samples were used as controls, and the mean genomic coverage was 3.83-fold. Data were aligned to the human genome, repetitive regions were removed, the remaining data were normalized for GC content, and z scores were calculated for the affected region.RESULTS:The median fetal DNA contribution for all samples was 18%, with the affected samples containing 17%-18% fetal DNA. Using a technique similar to that used for sequencing-based fetal aneuploidy detection from maternal plasma, we detected a statistically significant loss of representation of a portion of chromosome 22q11.2 in both of the affected fetal samples. No such loss was detected in any of the control samples.CONCLUSIONS:Noninvasive prenatal diagnosis of subchromosomal fetal genomic anomalies is feasible with next-generation sequencing.

• Neonatal Transcutaneous Bilirubin Measurements: An Opportunity to Enhance Laboratory Utilization and Improve Patient Care.

  Authors: M Jeffrey Maisels

  Clinical chemistry.

• Commentary.

  Authors: Mohit Jain, Jorge Plutzky

  Clinical chemistry. 58(5):829-30.

• A 69-Year-Old Man with Long-standing Thrombocytopenia.

  Authors: Martin Ehrenschwender, Juergen Koessler

  Clinical chemistry. 58(5):953-4.

• Polyphony.

  Authors: Patrick M M Bossuyt

  Clinical chemistry. 58(5):959.

• Parkin and Parkinson Disease.

  Authors: Hideki Shimura, Yoshikuni Mizuno, Nobutaka Hattori

  Clinical chemistry.

• A 54-year-old diabetic man with low serum cholesterol.

  Authors: Ugur Turk, Gunes Basol, Burcu Barutcuoglu, Fahri Sahin, Sara Habif, Patrizia Tarugi, Oya Bayindir

  Clinical chemistry. 58(5):826-9.

• Commentary.

  Authors: Alan T Remaley

  Clinical chemistry. 58(5):830.

• Lab on a stamp: paper-based diagnostic tools.

  Authors: Molly Webster, Vikram Sheel Kumar

  Clinical chemistry. 58(5):956-8.

• Observation and creativity: leonardo da vinci.

  Authors: Marek H Dominiczak

  Clinical chemistry. 58(5):960-1.

• Accuracy of First and Second Generation Testosterone Assays and Improvement through Sample Extraction.

  Authors: Wouter M Tiel Groenestege, Hong N Bui, Joop Ten Kate, Paul P C A Menheere, Wytze P Oosterhuis, Huib L Vader, Annemieke C Heijboer, Marcel J W Janssen

  Clinical chemistry.

• Increased Hemoglobin A1c in Obese Pregnant Women after Exclusion of Gestational Diabetes.

  Authors: Regina Ensenauer, Julia Gmach, Ina Nehring, Rüdiger von Kries

  Clinical chemistry.

• Plasma Prolylcarboxypeptidase (Angiotensinase C) is Increased in Obesity and Diabetes Mellitus and Related to Cardiovascular Dysfunction.

  Authors: Shengyuan Xu, Lars Lind, Linshu Zhao, Bertil Lindahl, Per Venge

  Clinical chemistry.

  BACKGROUND: Prolylcarboxypeptidase (PRCP) (angiotensinase C) has 3 major targets, angiotensin II, prekallikrein, and α-melanocyte stimulating hormone(1-13). The truncation of the latter leads to lossBACKGROUND: Prolylcarboxypeptidase (PRCP) (angiotensinase C) has 3 major targets, angiotensin II, prekallikrein, and α-melanocyte stimulating hormone(1-13). The truncation of the latter leads to loss in appetite regulation and obesity in experimental animals. The objectives of this study were to purify PRCP from a native source, establish a sensitive immunoassay for PRCP, and relate plasma PRCP concentrations to signs and symptoms of obesity, diabetes mellitus, and cardiovascular dysfunction.METHODS: Purification of PRCP from human neutrophils and establishment of a sensitive ELISA was carried out with the use of samples from study participants. Three cohorts were studied: healthy individuals (n = 40); a chest pain cohort (Fast Assessment of Thoracic Pain by Neural Networks) (n = 165); and a community-based cohort [Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)] (n = 1004).RESULTS: PRCP was purified to homogeneity. Mean (SD) plasma concentrations in healthy individuals were 12.9 (3.2) μg/L and were increased in patients with chest pain and in patients with obesity and/or diabetes mellitus (P < 0.0001). In the PIVUS cohort the concentrations were related to several measures of arterial plaque formation, thickness of arterial intima media and posterior wall of the heart (P = 0.04-0.000005); the Framingham score (r = 0.14, P < 0.0001); and concentrations of C-reactive protein (r = 0.16, P < 0.0001) and N-terminal pro B-type natriuretic peptide (r = -0.13, P < 0.0001).CONCLUSIONS: Plasma concentrations of PRCP may be used to reflect metabolic conditions in individuals with obesity and diabetes mellitus. The associations of PRCP concentrations with signs of cardiovascular dysfunction and cardiovascular abnormalities suggest a pivotal role of the enzyme in disease.

• Improving the Success and Reliability of Adrenal Venous Sampling: Focus on Intraprocedural Cortisol Measurement.

  Authors: Michael Stowasser

  Clinical chemistry.

• Cannabinoid Stability in Authentic Oral Fluid after Controlled Cannabis Smoking.

  Authors: Dayong Lee, Garry Milman, David M Schwope, Allan J Barnes, David A Gorelick, Marilyn A Huestis

  Clinical chemistry.

  BACKGROUND: Defining cannabinoid stability in authentic oral fluid (OF) is critically important for result interpretation. There are few published OF stability data, and of those available, allBACKGROUND: Defining cannabinoid stability in authentic oral fluid (OF) is critically important for result interpretation. There are few published OF stability data, and of those available, all employed fortified synthetic OF solutions or elution buffers; none included authentic OF following controlled cannabis smoking.METHODS: An expectorated OF pool and a pool of OF collected with Quantisal™ devices were prepared for each of 10 participants. Δ9-Tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), and cannabinol (CBN) stability in each of 10 authentic expectorated and Quantisal-collected OF pools were determined after storage at 4°C for 1 and 4 weeks and at -20°C for 4 and 24 weeks. Results within ±20% of baseline concentrations analyzed within 24 h of collection were considered stable.RESULTS: All Quantisal OF cannabinoid concentrations were stable for 1 week at 4°C. After 4 weeks at 4°C, as well as 4 and 24 weeks at -20°C, THC was stable in 90%, 80%, and 80% and THCCOOH in 89%, 40%, and 50% of Quantisal samples, respectively. Cannabinoids in expectorated OF were less stable than in Quantisal samples when refrigerated or frozen. After 4 weeks at 4 and -20°C, CBD and CBN were stable in 33%-100% of Quantisal and expectorated samples; by 24 weeks at -20°C, CBD and CBN were stable in ≤44%.CONCLUSIONS: Cannabinoid OF stability varied by analyte, collection method, and storage duration and temperature, and across participants. OF collection with a device containing an elution/stabilization buffer, sample storage at 4°C, and analysis within 4 weeks is preferred to maximize result accuracy.

• A Unique Approach to Business Strategy as a Means to Enable Change in Global Healthcare: A Case Study.

  Authors: Charles R Mace, Una S Ryan

  Clinical chemistry.

• The American Diabetes Association and the International Association of Diabetes and Pregnancy Study Groups Recommendations for Diagnosing Gestational Diabetes Should Be Used Worldwide.

  Authors: Donald R Coustan

  Clinical chemistry.

• Serum S100B Determination in the Management of Pediatric Mild Traumatic Brain Injury.

  Authors: Damien Bouvier, Mathilde Fournier, Jean-Benoît Dauphin, Flore Amat, Sylvie Ughetto, André Labbé, Vincent Sapin

  Clinical chemistry.

  BACKGROUND: The place of serum S100B measurement in mild traumatic brain injury (mTBI) management is still controversial. Our prospective study aimed to evaluate its utility in the largest childBACKGROUND: The place of serum S100B measurement in mild traumatic brain injury (mTBI) management is still controversial. Our prospective study aimed to evaluate its utility in the largest child cohort described to date.METHODS: Children younger than 16 years presenting at a pediatric emergency department within 3 h after TBI were enrolled prospectively for blood sampling to determine serum S100B concentrations. The following information was collected: TBI severity determined by using the Masters classification [1: minimal or Glasgow Coma Scale (GCS) 15, 2: mild or GCS 13-15, and 3: severe or GCS <13]; whether hospitalized or not; good or bad clinical evolution (CE); whether cranial computed tomography (CCT) was prescribed; and related presence (CCT+) or absence (CCT-) of lesions.RESULTS: For the 446 children enrolled, the median concentrations of S100B were 0.21, 0.31, and 0.44 μg/L in Masters groups 1, 2, and 3, respectively, with a statistically significant difference between these groups (P < 0.05). In Masters group 2, 65 CCT scans were carried out. Measurement of S100B identified patients as CCT+ with 100% (95% CI 85-100) sensitivity and 33% (95% CI 20-50) specificity. Of the 424 children scored Masters 1 or 2, 21 presented "bad CE." S100B identified bad CE patients with 100% (95% CI 84-100) sensitivity and 36% (95% CI 31-41) specificity. Of the 242 children hospitalized, 81 presented an S100B concentration within the reference interval.CONCLUSIONS: Serum S100B determination during the first 3 h of management of children with mTBI has the potential to reduce the number of CCT scans, thereby avoiding unnecessary irradiation, and to save hospitalization costs.

• MicroRNAs Regulate Expression of Oncogenes.

  Authors: Frank J Slack

  Clinical chemistry.

• Hyperglycosylated Human Chorionic Gonadotropin in Serum of Testicular Cancer Patients.

  Authors: Anna Lempiäinen, Kristina Hotakainen, Carl Blomqvist, Henrik Alfthan, Ulf-Håkan Stenman

  Clinical chemistry.

  BACKGROUND: Hyperglycosylated human chorionic gonadotropin (hCG-h) contains larger and more complex carbohydrate chains than regular human chorionic gonadotropin (hCG). hCG-h is thought to be theBACKGROUND: Hyperglycosylated human chorionic gonadotropin (hCG-h) contains larger and more complex carbohydrate chains than regular human chorionic gonadotropin (hCG). hCG-h is thought to be the major form of hCG produced by testicular cancers and it has been suggested to play a key role in tumor invasion, but studies on hCG-h in testicular cancer are limited. We studied whether serum hCG is hyperglycosylated, and whether measurement of hCG-h in serum offers clinical value in the management of testicular cancer.METHODS: We determined the serum concentrations of hCG-h, hCG, and the free β subunit of hCG (hCGβ) by time-resolved immunofluorometric assays in 176 serum samples (preoperative n = 67, relapse n = 20, follow-up n = 89) obtained from 84 testicular cancer patients. We analyzed the association between preoperative serum concentrations of hCG, hCG-h, and hCGβ with known prognostic factors and progression-free survival time.RESULTS: A major proportion of hCG was hyperglycosylated preoperatively, at relapse, and shortly after treatment. The serum concentrations of hCG-h and hCG correlated strongly with each other and had similar diagnostic value. The preoperative serum concentration of hCG-h correlated with prognostic factors and outcome in the same way as hCG. Increased preoperative hCGβ concentration predicted shorter progression-free survival.CONCLUSIONS: Most of the hCG expressed by testicular cancers is hyperglycosylated and therefore it is important that hCG assays used for management of testicular cancer recognize hCG-h.

• Elementary, My Dear Doctor Watson.

  Authors: Ramy Arnaout

  Clinical chemistry.

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.