Laboratory Test Abnormalities are Common in Polymyositis and Dermatomyositis and Differ Among Clinical and Demographic Groups

Objective: Given the difficulties regarding the interpretation of common laboratory test results in polymyositis (PM) and dermatomyositis (DM) in clinical practice, we assessed their range of abnormalities, differences among phenotypes and interrelationships in a large referral population.Methods: We retrospectively assessed 20 commonly measured blood laboratory tests in 620 well-defined PM/DM patients at different stages of illness and treatment to determine the frequency, range of abnormalities and correlations among clinical, gender, racial and age phenotypes.Results: Myositis patients at various stages of their disease showed frequent elevations of the serum activities of creatine kinase (51%), alanine aminotransferase (43%), aspartate aminotransferase (51%), lactate dehydrogenase (60%), aldolase (65%) and myoglobin levels (48%) as expected. Other frequent abnormalities, however, included elevated high white blood cell counts (36%), low lymphocyte counts (37%), low hematocrit levels (29%), low albumin levels (22%), high creatine kinase MB isoenzyme fractions (52%), high erythrocyte sedimentation rates (33%) and high IgM and IgG levels (16% and 18%, respectively). Many of these tests significantly differed among the clinical, gender, racial and age groups. Significant correlations were also found among a number of these laboratory tests, particularly in the serum activity levels of creatine kinase, the transaminases, lactate dehydrogenase and aldolase.Conclusion: Laboratory test abnormalities are common in PM/DM. Knowledge of the range of these expected abnormalities in different myositis phenotypes, gender and age groups and their correlations should assist clinicians in better interpretation of these test results, allow for a clearer understanding what level of abnormality warrants further evaluation for liver or other diseases, and may avoid unnecessary laboratory or other testing

Serum proteins and paraproteins in women with silicone implants and connective tissue disease: a case–control study

Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but did not control for the presence of connective-tissue disease (CTD). This retrospective case–control study, performed in tertiary-care academic centers, assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four women with silicone implants who subsequently developed CTD, and 74 age-matched and CTD-matched women without silicone implants, were assessed in the primary study; other groups were used for additional comparisons. Routine serum protein determinations and high-sensitivity protein electrophoresis and immunofixation electrophoresis were performed for detection of paraproteins. Women with silicone implants, either with or without CTD, had significantly lower serum total protein and α1-globulin, α2-globulin, β-globulin, γ-globulin, and IgG levels compared with those without silicone implants. There was no significant difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age-matched and CTD-matched women without silicone implants (5.4%) (odds ratio, 1.82; 95% confidence interval, 0.51–6.45). Paraprotein isotypes were similar in the two groups, and the clinical characteristics of the 13 women with paraproteinemia were comparable with an independent population of 10 women with silicone breast implants, CTD, and previously diagnosed monoclonal gammopathies. In summary, this first comprehensive study of serum proteins in women with silicone implants and CTD found no substantially increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require further investigation

Rapid and/or high-throughput genotyping for human red blood cell, platelet and leukocyte antigens, and forensic applications

Traditionally, transfusion medicine, platelet and human leukocyte antigen (HLA) typing, and forensic medicine relied on serologic studies. In recent years, molecular testing on nucleic acids has been increasingly applied to these areas. Although conventional molecular diagnostic methods such as PCR-sequence-specific priming, PCR-restriction fragment-length polymorphism, PCR-single-strand conformation polymorphism, sequence-based typing, and DNA fingerprinting have been shown to perform well, their use is limited by long turnaround times, high cost, labor-intensiveness, the need for special technical skills, and/or the high risk of amplicon contamination. With advance of fast and/or high-throughput methods and platforms that often combine amplification and detection, a new era of molecular genotyping is emerging in these fields dominated by serology for a century. As new targets, short tandem repeats, mitochondrial DNA and Y-chromosome sequences were introduced for forensic applications. This article reviews the current status of the application of rapid and/or high-throughput genotyping methods to these areas. The results are already promising with real-time PCR, pyrosequencing, microarrays, and mass spectrometry and show high concordance rates with classic serologic and earlier manual molecular diagnostic methods. Exploration of other emerging methodologies will likely further enhance the diagnostic utility of molecular testing in these areas

Hawthorne Effect with Transient Behavioral and Biochemical Changes in a Randomized Controlled Sleep Extension Trial of Chronically Short-Sleeping Obese Adults: Implications for the Design and Interpretation of Clinical Studies

<div><p>Objective</p><p>To evaluate the effects of study participation <i>per se</i> at the beginning of a sleep extension trial between screening, randomization, and the run-in visit.</p><p>Design</p><p>Subjects were screened, returned for randomization (Comparison <i>vs.</i> Intervention) after 81 days (median), and attended run-in visit 121 days later.</p><p>Setting</p><p>Outpatient.</p><p>Patients</p><p>Obese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6±19.7 kg, <6.5 h sleep/night.</p><p>Intervention</p><p>Non-pharmacological sleep extension.</p><p>Measurements</p><p>Sleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids.</p><p>Results</p><p>Prior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 ±51.2 <i>vs.</i> 388.1±48.6 min/night; mean±SD; P<0.001 screening vs. randomization; actigraphy: 344.3 ±41.9 <i>vs.</i> 358.6±48.2 min/night; P<0.001) sleep quality improved (9.1±3.2 <i>vs.</i> 8.2±3.0 PSQI score; P<0.001), sleepiness tended to improve (8.9±4.6 <i>vs.</i> 8.3±4.5 ESS score; P = 0.06), insulin resistance decreased (0.327±0.038 <i>vs.</i> 0.351±0.045; Quicki index; P<0.001), and lipids improved, except for HDL-C. Abnormal fasting glucose (25% <i>vs.</i> 11%; P = 0.007), and metabolic syndrome (42% <i>vs.</i> 29%; P = 0.007) both decreased. In absence of intervention, the earlier metabolic improvements disappeared at the run-in visit.</p><p>Limitations</p><p>Relatively small sample size.</p><p>Conclusions</p><p>Improvements in biochemical and behavioral parameters between screening and randomization changed the “true” study baseline, thereby potentially affecting outcome. While regression to the mean and placebo effect were considered, these findings are most consistent with the “Hawthorne effect”, according to which behavior measured in the setting of an experimental study changes in response to the attention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/show/NCT00261898" target="_blank">NCT00261898</a>.</p></div

Study flow diagram.

<p>Study flow diagram.</p

Characteristics at screening (Visit 1) of participants who completed randomization.

<p>(Visit 2) and run-in (Visit 3).</p><p>Data is reported as mean±SD or count (frequency).</p><p><b>*: P<0.05</b>.</p>1<p>Daytime sleepiness (ESS score): a score of 10 or more is considered sleepy.</p>2<p>Subjective sleep quality (PSQI score): a score of 5 or more is considered abnormal.</p