Observer variability in the evaluation of dual-isotope Tl-201/Tc-99m sestamibi rest/stress myocardial perfusion SPECT in men and women with known or suspected stable angina pectoris

BACKGROUND: Observer variability of dual-isotope myocardial perfusion imaging (MPI) with single photon emission computed tomography has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. METHODS AND RESULTS: We report on 507 patients with known or suspected stable angina who were studied before coronary angiography. A 1-day thallium 201/technetium 99m sestamibi rest/stress MPI protocol was used. MPI was interpreted by 2 independent observers without knowledge of clinical data, using a 20-segment scoring model. By consensus, the overall rate of abnormal MPI was 49% (59% in men and 34% in women). The interobserver agreement for the whole group (kappa = 0.85) and for men and women separately (kappa = 0.86 and 0.82, respectively) was excellent with regard to the overall diagnosis (normal, reversible, or fixed defects) as well as left anterior descending and left circumflex artery vascular territories (kappa = 0.85 and 0.82, respectively). However, in the right coronary artery territory, agreement was excellent in men (kappa = 0.83) but moderate in women (kappa = 0.57). CONCLUSIONS: In a relatively large group of men and women with stable angina pectoris, interpretive reproducibility (overall and individual vessel diagnosis) was excellent, except in the right coronary artery territory of women, in which it was moderate.     

Long-Term Follow-up After Embolization of Pulmonary Arteriovenous Malformations with Detachable Silicone Balloons

Long-term follow-up results after embolization of 13 pulmonary arteriovenous malformations in 10 patients by use of 14 detachable silicone balloons are given. Patients were followed for a mean of 99 months (range, 63–123 months) with chest x-rays and for a mean of 62 months (range, 3–101 months) with pulmonary angiography. Fifty-four percent of the balloons were deflated at latest radiographic chest film follow-up, but at pulmonary angiographic follow-up all embolized malformations were without flow irrespective of whether or not the balloons were visible. Detachable silicone balloons are not available anymore, but use of these balloons for embolization of pulmonary arteriovenous malformations has been shown to be a safe and precise method, with immediate occlusion of the feeding artery and with long-lasting occlusion, even though many balloons deflate with time, leaving a fibrotic scar replacing the pulmonary arteriovenous malformation. No case of recanalization has been discovered, and these results seem to justify a reduced number of controls of these balloon-embolized malformations.     

Acute effects of smoking on left ventricular function and neuro-humoral responses in patients with known or suspected ischaemic heart disease

Systolic left ventricular function was examined by radionuclide ventriculography in 12 habitual smokers with known or suspected ischaemic heart disease, aged 33-69 years, before, during, and after smoking of two cigarettes in a row and was repeated on a non-smoking control day. Plasma concentrations of adrenaline, noradrenaline, renin, and angiotensin II were determined on the smoking day, before and immediately after smoking. During smoking, there were significant increases in heart rate (+27%), rate-pressure product (+23%), and cardiac output (+14%) in the face of a significant increase in left ventricular end-systolic volume (+5%) and significant decreases in ejection fraction (-6%) and stroke volume (-8%). Blood pressure was virtually unchanged, and total peripheral resistance remained constant. Plasma adrenaline increased by 100%, renin decreased by 21%, and noradrenaline and angiotensin II did not change. The humoral changes were not correlated to changes in any of the haemodynamic variables. Areas of myocardial hypokinesis emerged or widened during smoking in 11 of 12 patients. Thus, in patients with known or suspected ischaemic heart disease, smoking was associated with an acute decrease in systolic ventricular function and development of widespread hypokinesis despite adrenaline stimulation.     

Simultaneous measurement of 25 inflammatory markers and neurotrophins in neonatal dried blood spots by immunoassay with xMAP technology

BACKGROUND: Inflammatory reactions and other events in early life may be part of the etiology of late-onset diseases, including cerebral palsy, autism, and type 1 diabetes. Most neonatal screening programs for congenital disorders are based on analysis of dried blood spot samples (DBSS), and stored residual DBSS constitute a valuable resource for research into the etiology of these diseases. The small amount of blood available, however, limits the number of analytes that can be determined by traditional immunoassay methodologies. METHODS: We used new multiplexed sandwich immunoassays based on flowmetric Luminex xMAP technology to measure inflammatory markers and neutrophins in DBSS. RESULTS: The high-capacity 25-plex multianalyte method measured 23 inflammatory and trophic cytokines, triggering receptor expressed on myeloid cells-1 (TREM-1), and C-reactive protein in two 3.2-mm punches from DBSS. It also measured 26 cytokines and TREM-1 in serum. Standards Recovery in the 25-plex method were 90%-161% (mean, 105%). The low end of the working range for all 25 analytes covered concentrations found in DBSS from healthy newborns. Mean recovery of exogenous analytes added at physiologic concentrations in DBSS models was 174%, mean intra- and interassay CVs were 6.2% and 16%, respectively, and the mean correlation between added and measured analytes was r2 = 0.91. In DBSS routinely collected on days 5-7 from 8 newborns with documented inflammatory reactions at birth, the method detected significantly changed concentrations of inflammatory cytokines. Measurements on DBSS stored at -24 degrees C for >20 years showed that most cytokines are detectable in equal concentrations over time. CONCLUSIONS: The method can reliably measure 25 inflammatory markers and growth factors in DBSS. It has a large potential for high-capacity analysis of DBSS in epidemiologic case-control studies and, with further refinements, in neonatal screening.     

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase.

This paper is the fourth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 2.     

The European Narcolepsy Network (EU‐NN) database

Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease‐specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web‐based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post‐marketing medication side‐effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.     

Effect of Inflammation in the Periodontium in Early Old Age on Mortality at 21-Year Follow-Up

OBJECTIVES: To analyze whether inflammatory processes in the periodontium in early old age are related to subsequent mortality during 21 years of follow-up in a nondisabled 70-year-old population.
SETTING: Community-based population in Copenhagen.
DESIGN: The study was based on the Glostrup Aging Study of the 1914 population, with baseline in 1984 when the participants were 70 years old and follow-up 21 years later.
PARTICIPANTS: Three hundred thirty-five dentate men and women participated in the clinical oral health examination.
MEASUREMENTS: Severe periodontal inflammation was measured for all teeth present as the number of teeth with inflammation and periodontal pockets 6 mm deep or more. Mortality data were obtained from the Danish Death Register at 21-year follow-up. The Cox proportional hazards regression model was used. Covariates were measured at baseline and included number of teeth, caries, sex, education, income, hypertension, diabetes mellitus, osteoarthritis, arteriostenosis, myocardial infarction, comorbidity, fatigue, and ability to brush teeth.
RESULTS: The analyses showed that severe periodontal inflammation in at least three teeth at age 70 was marginally related to mortality during 21-year follow-up (crude hazard ratio (HR)=1.17, 95% confidence interval (CI)=0.91–1.78). The estimate increased slightly when adjusted for sex, income, fatigue, and smoking (adjusted HR=1.37, 95% CI=0.97–1.92). The estimates were attenuated when adjusted for the specific diseases, especially arteriostenosis and osteoarthritis.
CONCLUSION: Inflammation in the periodontium in early old age tends to be associated with mortality in older age.     

Evaluation of the genotoxic potential of 3-monochloropropane-1,2-diol (3-MCPD) and its metabolites, glycidol and beta-chlorolactic acid, using the single cell gel/comet assay.

3-monochloropropane-1,2-diol (3-MCPD) is a member of a group of chemicals known as chloropropanols. It is found in many foods and food ingredients as a result of food processing. 3-MCPD is regarded as a rat carcinogen known to induce Leydig-cell and mammary gland tumours in males and kidney tumours in both genders. The aim of our study was to clarify the possible involvement of genotoxic mechanisms in 3-MCPD induced carcinogenicity at the target organ level. For that purpose, we evaluated DNA damages in selected target (kidneys and testes) and non-target (blood leukocytes, liver and bone marrow) male rat organs by the in vivo alkaline single cell gel electrophoresis (comet) assay, 3 and 24 h after 3-MCPD oral administration to Sprague-Dawley and Fisher 344 adult rats. 3-MCPD may be metabolised to a genotoxic intermediate, glycidol, whereas the predominant urinary metabolite in rats following 3-MCPD administration is beta-chlorolactic acid. Therefore, we also studied the DNA damaging effects of 3-MCPD and its metabolites, glycidol and beta-chlorolactic acid, in the in vitro comet assay on CHO cells. Our results show the absence of genotoxic potential of 3-MCPD in vivo in the target as well as in the non-target organs. Glycidol, the epoxide metabolite, induced DNA damages in CHO cells. beta-Chlorolactic acid, the main metabolite of 3-MCPD in rats, was shown to be devoid of DNA-damaging effects in vitro in mammalian cells.