Shorter sleep duration is associated with higher energy intake and an increase in BMI z-score in young children predisposed to overweight.

BACKGROUND: Inadequate sleep has been shown to be a contributor to obesity in both children and adults. Less evidence is available for toddlers and among those with higher obesity risk. The objective of this study was to examine the relationship between sleep patterns and body weight development in a group of young obesity-predisposed children, and to assess whether intakes of energy or macronutrients mediate this relationship. METHODS: Participants included 368 Danish children aged 2-6 years from the Healthy Start Study, a 1.3 year randomised controlled intervention trial. Sleep habits were measured using a 7-day sleep diary. Multivariate linear regression with adjustment for confounders was used to assess the association of sleep duration and sleep variability with 1.3 year changes (Δ) in body mass index (BMI) z-score from baseline to follow-up. RESULTS: The average nighttime sleep duration was 10.7 h (range 8.8-12.5 h). After controlling for potential confounders, a significant inverse association between nighttime sleep duration and ΔBMI z-score (ß=-0.090, P=0.046) was observed. This relationship was mediated by energy intake, with all macronutrients contributing to this mediation effect. No associations were found for sleep variability and ΔBMI z-score but baseline intake of added sugars and sugary beverages were positively associated with sleep variability. CONCLUSION: Shorter sleep duration, mediated by energy intake in early in life, seems a risk factor for weight gain among young obesity-predisposed children.

Repository corticotrophin injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids.

Repository corticotrophin injection (RCI, H.P Acthar® gel) has been approved for use in the management of multiple autoimmune and inflammatory diseases for more than a half-century, but its mechanism of action is not well understood. We used RNA-Seq methods to define RCI-regulated mRNAs in cultured human B cells under conditions of activation by interleukin (IL)-4 and CD40 ligand. Following IL-4/CD40L activation and RCI treatment we found up-regulation of 115 unique mRNA transcripts and down-regulation of 80 unique mRNAs. The effect on these RNA levels was dose-dependent for RCI and was distinct from changes in mRNA expression induced by treatment with a potent synthetic glucocorticoid. RCI down-regulated mRNAs were observed to include a significant over-representation of genes critical for B cell proliferation under activating conditions. These data confirm that RCI exerts direct effects on human B cells to modulate mRNA expression in specific pathways of importance to B cell function and that, at the molecular level, the effects of RCI are distinct from those exerted by glucocorticoids.

Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants.

Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk. Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear. The majority of the human genome is transcribed yet its biologic significance is incompletely understood. We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders. We found that loci transcribing novel lncRNAs were not randomly distributed across the genome but co-localized with leukocyte transcriptional enhancers, especially super-enhancers, and near genetic variants associated with autoimmune disease risk. We propose that alterations in enhancer function, including lncRNA expression, produced by genetics and environment, change cellular phenotypes contributing to disease risk and pathogenesis and represent attractive therapeutic targets.

Sugar-sweetened beverages consumption in relation to changes in body fatness over 6 and 12 years among 9-year-old children: the European Youth Heart Study.

BACKGROUND/OBJECTIVES: In parallel with the obesity epidemic, consumption of sugar-sweetened beverages (SSB) has risen over the same period. Our aim was to investigate associations between the consumption of SSB in childhood and adolescence with subsequent changes in body fatness in early adulthood. SUBJECTS/METHODS: A longitudinal study of 9-year-old children (n=283) enrolled in the Danish part of the European Youth Heart Study with a 6-year and 12-year follow-up. Data were collected at ages 9, 15 and 21 years. Multivariate regression analyses with adjustment for potential confounders were used to evaluate the effect of SSB consumption at 9 and 15 years and change in SSB consumption from 9-15 years on subsequent change in body fatness until 21 years. RESULTS: Subjects who consumed more than one serve of SSB daily at age 15 years had larger increases in body mass index (BMI) (ß=0.92, P=0.046) and waist circumference (WC) (ß=2.69, P=0.04) compared to non-consumers over the subsequent 6 years. In addition, subjects who increased their SSB consumption from age 9-15 years also had larger increases in BMI (ß=0.91, P=0.09) and WC (ß=2.72, P=0.04) from 15-21 years, compared to those who reported no change in consumption. No significant association was observed from 9-21 years. CONCLUSION: This study provides new evidence that SSB consumption in adolescence and changes in SSB consumption from childhood to adolescence are both significant predictors of change in body fatness later in early adulthood.

No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene.

UNLABELLED: Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men. INTRODUCTION: There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007. METHODS: The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture. RESULTS: Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97). CONCLUSIONS: This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.

Malignant mesotheliomas in former miners and millers of crocidolite at Wittenoom (Western Australia) after more than 50 years follow-up.

BACKGROUND: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2008, to compare this with earlier predictions, and to relate the mesothelioma rate to amount of exposure. METHODS: A group of 6489 men and 419 women who had worked for the company operating the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2008. RESULTS: The cumulative number of mesotheliomas up to 2008 was 316 in men (268 pleural, 48 peritoneal) and 13 (all pleural) in women. There had been 302 deaths with mesothelioma in men and 13 in women, which was almost 10% of all known deaths. Mesothelioma rate, both pleural and peritoneal, increased with time since first exposure and appeared to reach a plateau after about 40 to 50 years. The mesothelioma rate increased with amount of exposure and the peritoneal mesotheliomas occurred preferentially in the highest exposure group, 37% compared with 15% overall. CONCLUSION: By the end of 2008, the number of mesothelioma deaths had reached 4.7% for all the male workers and 3.1% for the females. Over the past 8 years the numbers were higher than expected. It is predicted that about another 60 to 70 deaths with mesothelioma may occur in men by 2020.

Gene-expression signatures: biomarkers toward diagnosing multiple sclerosis.

Identification of biomarkers contributing to disease diagnosis, classification or prognosis could be of considerable utility. For example, primary methods to diagnose multiple sclerosis (MS) include magnetic resonance imaging and detection of immunological abnormalities in cerebrospinal fluid. We determined whether gene-expression differences in blood discriminated MS subjects from comparator groups, and identified panels of ratios that performed with varying degrees of accuracy depending upon complexity of comparator groups. High levels of overall accuracy were achieved by comparing MS with homogeneous comparator groups. Overall accuracy was compromised when MS was compared with a heterogeneous comparator group. Results, validated in independent cohorts, indicate that gene-expression differences in blood accurately exclude or include a diagnosis of MS and suggest that these approaches may provide clinically useful prediction of MS.

25-Hydroxyvitamin D levels in African-American and Caucasian/Hispanic subjects with cutaneous lupus erythematosus.

BACKGROUND: Because exposure to ultraviolet radiation accounts for a significant portion of endogenous vitamin D production, subjects with cutaneous lupus (CLE) who practise sun-protective measures are at risk for vitamin D insufficiency. Previous studies have shown light-skinned subjects with CLE to have lower serum 25-hydroxy (25-OH) vitamin D levels than normal controls. OBJECTIVES: To assess the status of vitamin D insufficiency in dark-skinned individuals with CLE. METHODS: We performed a cross-sectional study comparing serum 25-OH vitamin D levels in 25 African-American (AA) subjects with CLE and 26 normal AA subjects matched by age, sex and season in Dallas, Texas. A questionnaire on demographics, medical history and lifestyle habits was administered to determine factors potentially affecting vitamin D levels. Findings were contrasted to a similar comparison in 26 Caucasian and Hispanic (C/H) subjects with CLE and 24 normal C/H subjects matched by age, sex and season. RESULTS: We found similar mean±SD 25-OH vitamin D levels in AA subjects with CLE (52·0±18·5nmolL(-1) ) and normal AA subjects (54·8±21·2 nmolL(-1) ) (P=0·62). Almost half of AA subjects in both groups were vitamin D insufficient. A larger difference in 25-OH vitamin D levels was found between C/H subjects with CLE (59·4±21·0nmolL(-1) ) and normal C/H subjects (70·5±27·4nmolL(-1) ) (P=0·12). Two-way anova demonstrated that skin colour (AA vs. C/H) had a significant effect on 25-OH vitamin D levels (P=0·008), although CLE status (CLE vs. normal) did not (P=0·13). CONCLUSIONS: Providers are encouraged to address vitamin D insufficiency concerns in all dark-skinned individuals. Future studies should stratify subjects by skin colour in determining differences between subjects with CLE and normal controls.

Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus.

Up to 28% of patients with discoid lupus erythematosus (DLE) are susceptible to developing systemic lupus erythematosus (SLE). To better characterize patients with DLE who have a higher potential of developing SLE, we reviewed studies contrasting, firstly, DLE-only patients (i.e. patients with DLE without SLE) and SLE patients with DLE (i.e. patients who are diagnosed with SLE and DLE simultaneously, and patients with SLE who later develop DLE), and secondly, DLE-only patients and patients with DLE who progress to SLE. These studies have commonly identified various clinical and laboratory indicators, such as widespread DLE lesions, arthralgias/arthritis, nail changes, anaemia, leucopenia, high erythrocyte sedimentation rates (ESRs) and high titres of antinuclear antibodies (ANAs), which are associated with progression to SLE in patients with DLE, and SLE patients with DLE. Limitations of these studies include inadequate follow-up time, small numbers of patients with DLE converting to SLE, outdated criteria for SLE diagnosis and retrospective study designs. However, because of the risk of SLE development in patients with DLE, complete skin examinations, joint assessments and laboratory tests including ANA, ESR and full blood counts should be performed regularly for patients with DLE. A prospective study following patients with DLE who do or do not develop SLE is currently underway through the Cutaneous Lupus Registry at the University of Texas Southwestern Medical Center. It will seek to identify clinical features and biomarkers that improve our assessment of risk of systemic spread in these patients.

Elevated IgG autoantibody production in oligoarticular juvenile idiopathic arthritis may predict a refractory course.

OBJECTIVES: Although oligoarticular juvenile idiopathic arthritis (oJIA) is considered to carry the best prognosis among the JIA subtypes, many children evolve to a chronic course. A few studies have identified clinical risk factors for disease extension, and recent studies have evaluated synovial fluid markers. However, the only biological marker from the serum studied to date is the anti-nuclear antibody (ANA), regarding which there is mixed data regarding prognosis. No studies have evaluated whether additional autoantibodies may affect the articular prognosis of oJIA. METHODS: Microarrays containing candidate autoantigens were printed on slides, which were used to profile 36 children with oJIA and 18 controls. Unsupervised cluster analysis was used to identify distinct subgroups of JIA patients. Response to therapy after a mean interval of 4.9 months was evaluated. RESULTS: Cluster analysis revealed two subgroups of oJIA patients, with identical clustering observed when children with onset over age six were excluded. Cluster 1 had higher levels of multiple autoantibodies compared to both cluster 2 as well as controls, including antibodies against several extracellular matrix (ECM) and nuclear antigens. Although the two patient clusters were similar with respect to clinical features and treatment decisions, children in cluster 1 were less likely to have attained remission by the follow-up visit. CONCLUSIONS: Antibodies against ECM and possibly other antigens may identify a sub-group of children with oJIA who will require more aggressive therapy to attain control of the arthritis.

Nutraceuticals for the treatment of osteoarthritis.

Osteoarthritis (OA) is a highly prevalent human condition which is becoming an even greater health problem in an aging global population. Existing treatments for OA provide pain relief and some anti-inflammatory effects, but no truly disease-modifying treatments are available for this disease. Furthermore, the generally advanced age and frequent comorbid conditions present in OA patients limit safety of many available drugs. Treatments with enhanced safety margins and that offer chondroprotective effects are unmet needs. Nutraceuticals derived from foods and herbs have been long used in traditional medicine, and many have wide-ranging biologic effects suggesting novel mechanisms of action. Some of these have shown promise in controlled clinical trials in OA patients. Whether these approaches could offer safe symptom relief and possibly mediate beneficial joint remodeling in early OA are possibilities that merit further investigation.

Interferon signature gene expression is correlated with autoantibody profiles in patients with incomplete lupus syndromes.

Interferon (IFN) signature genes have been shown to be expressed highly in peripheral blood of patients with systemic lupus erythematosus (SLE), especially in the presence of active disease. However, the expression of this gene signature in individuals with incomplete forms of lupus and the pathogenic relationship between IFN signature genes and autoantibody production have not been explored fully. In the present study, we examined the gene expression and autoantibody profiles of patients diagnosed with incomplete lupus erythematosus (ILE) to determine correlations of the gene expression signature with autoantibody production. Gene expression analysis was carried out on the 24K Illumina Human Refseq-8 arrays using blood samples from 84 subjects, including patients with SLE (n = 27) or ILE (n = 24), first-degree relatives (FDR) of these patients (n = 22) and non-autoimmune control (NC) individuals (n = 11). Autoantibody expression was measured using standard immunoassays and autoantigen proteomic arrays. Up-regulation of a set of 63 IFN signature genes was seen in 83% of SLE patients and 50% of ILE patients. High levels of IFN gene expression in ILE and SLE showed significant correlations with the expression of a subset of IgG autoantibodies, including chromatin, dsDNA, dsRNA, U1snRNP, Ro/SSA, La/SSB, topoisomerase I and Scl 70, while low IFN levels were correlated with immunoglobulin (Ig)M autoreactivity. These studies suggest that in patients with ILE the IFN gene expression signature may identify a subset of these individuals who are at risk for disease progression. Furthermore, high levels of alpha IFN may promote autoantibody class-switch from IgM to the more pathogenic IgG class.

Intake of calorically sweetened beverages and obesity.

The prevalence of obesity has increased in the past 30 years, and at the same time a steep increase in consumption of soft drinks has been seen. This paper reviews the literature for studies on associations between intake of calorically sweetened beverages and obesity, relative to adjustment for energy intake. Conclusions from previous reviews have been inconsistent, but some included many cross-sectional studies or studies supported by sugar industry. A literature search was performed for prospective and experimental studies using Medline and Scirus. Fourteen prospective and five experimental studies were identified. The majority of the prospective studies found positive associations between intake of calorically sweetened beverages and obesity. Three experimental studies found positive effects of calorically sweetened beverages and subsequent changes in body fat. Two experimental studies did not find effects. Eight prospective studies adjusted for energy intake. Seven of these studies reported associations that were essentially similar before and after energy adjustment. In conclusion, a high intake of calorically sweetened beverages can be regarded as a determinant for obesity. However, there seems to be no support that the association between intake of calorically sweetened beverages and obesity is mediated via increased energy intake, and alternative biological explanations should be explored.

Mortality of former crocidolite (blue asbestos) miners and millers at Wittenoom.

BACKGROUND: Blue asbestos was mined and milled at Wittenoom in Western Australia between 1943 and 1966. METHODS: Nearly 7000 male workers who worked at the Wittenoom mine and mill have been followed up using death and cancer registries throughout Australia and Italy to the end of 2000. Person-years at risk were derived using two censoring dates in order to produce minimum and maximum estimates of asbestos effect. Standardised mortality ratios (SMRs) compare the mortality of the former Wittenoom workers with the Western Australian male population. RESULTS: There have been 190 cases of pleural and 32 cases of peritoneal mesothelioma in this cohort of former workers at Wittenoom. Mortality from lung cancer (SMR = 1.52), pneumoconiosis (SMR = 15.5), respiratory diseases (SMR = 1.58), tuberculosis (SMR = 3.06), digestive diseases (SMR = 1.47), alcoholism (SMR = 2.24) and symptoms, signs and ill defined conditions (SMR = 2.00) were greater in this cohort compared to the Western Australian male population. CONCLUSION: Asbestos related diseases, particularly malignant mesothelioma, lung cancer and pneumoconiosis, continue to be the main causes of excess mortality in the former blue asbestos miners and millers of Wittenoom.

Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes.

The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.

Highly conserved gene expression profiles in humans with allergic rhinitis altered by immunotherapy.

BACKGROUND: Atopic diseases, resulting from hypersensitivity to a wide variety of allergens, affect 10-20% of the population. Immunotherapy is an effective treatment for atopic diseases, but its mechanisms are not fully understood. OBJECTIVE: We studied gene expression profiles in the peripheral blood mononuclear cells (PBMC) and examined whether the individuals with allergic rhinitis (AR) have a unique gene expression profile and how the immunotherapy affect the gene expression profiles. METHODS: We used cDNA microarray and 'expression analysis systemic explorer' to examine the gene expression profiles in the PBMC of atopic subjects and other groups. RESULTS: We identified a highly conserved gene expression profile in atopic subjects that permitted their accurate segregation from control or autoimmune subjects. A major feature of this profile was the under-expression of a variety of genes that encode proteins required for apoptosis and over-expression of genes that encode proteins critical for stress responses and signal transduction. We also identified 563 genes that can segregate individuals with AR based upon receipt of immunotherapy. CONCLUSION: There is a highly conserved gene expression profile in the PBMC of individuals with AR. This profile can be used to identify individuals with AR and to evaluate responses to immunotherapy. Quantitative endpoints, such as gene expression, may assist clinicians faced with clinical decisions in the diagnosis of patients and the evaluation of response to therapy. The knowledge of the possible genetic basis for immunotherapy efficacy may also lead to novel therapeutic approaches for atopic diseases.

Malignant pleural and peritoneal mesotheliomas in former miners and millers of crocidolite at Wittenoom, Western Australia.

AIMS: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2000, and to compare this with earlier predictions. METHODS: A group of 6493 men and 415 women who had worked at the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2000. RESULTS: The cumulative number of mesotheliomas up to 2000 was 235 in men (202 pleural, 33 peritoneal) and seven (all pleural) in women. There had been 231 deaths with mesothelioma (9% of known deaths). CONCLUSIONS: The number of deaths in men with mesothelioma between 1987 and 2000 was at the low end of the predictions made earlier based on the number of cases to 1986. If this trend continues, it is predicted that about another 110 deaths with mesothelioma will occur in men by 2020.

Bone marrow stromal cells mediate androgenic suppression of B lymphocyte development.

Castration of normal male mice induces expansion of the bone marrow B cell population, an effect that can be reversed by androgen replacement. We employed in vitro cultures and two in vivo models to investigate whether androgens exert these effects directly on marrow lymphoid precursors or whether actions on marrow stromal elements are required. Immature B cells from normal mouse bone marrow were not responsive to the suppressive effect of androgens unless they were cocultured with marrow stromal cells or with supernatants from androgen-treated stromal cells, suggesting that the androgen effects are exerted through marrow stromal elements by production of a diffusible mediator. Further experiments revealed that bone marrow stromal cells produced TGF-beta in response to dihydrotestosterone (DHT), and neutralization of TGF-beta in the DHT-treated stromal cells reversed the suppressive effects. The stromal cell requirement for androgen-mediated effects was confirmed in vivo by experiments using chimeric animals created by bone marrow transplantation in which androgen receptor expression was restricted to either the stromal or lymphoid cells of the bone marrow. Androgens only affected B cell development in chimeric mice with androgen-sensitive stromal cells. These experiments suggest that effects of androgens on developing B cells are mediated through androgen receptors in bone marrow stromal cells. TGF-beta is a candidate mediator for these hormonal effects.

Effects of androgens on T and B lymphocyte development.

The sexually dimorphic nature of normal immune responses and the remarkably higher incidence of autoimmune diseases in females have suggested a role for gonadal steroid hormones as modulators of immune system function. We have investigated the effects of androgens on the development of lymphocytes in the thymus and bone marrow. Expression of the androgen receptor, the ligand-activated transcription factor that mediates hormone actions, has been documented in lymphoid and nonlymphoid cells of thymus and bone marrow, but not in mature peripheral lymphocytes. This expression pattern suggests that the major impact of androgens must be on the developmental maturation of T and B lymphocytes rather than on the mature effector cells. Recent experiments have explored whether developing lymphoid precursors are the direct targets of androgen action or whether supporting cells, such as thymic epithelial cells and bone marrow stromal cells, are required for the receptor-mediated effects of androgens on lymphoid cell development. Bone marrow transplantation techniques using an androgen-resistant mouse strain permit the creation of chimeric mice with androgen receptor-defective lymphoid or epithelial/stromal cellular compartments. Hormonal manipulation experiments in these chimeric animals have suggested that thymic epithelial cells and bone marrow stromal cells are mediators of androgenic effects on immature lymphocytes. The long-range goal of these studies is to understand the basis for the disproportionate occurrence of autoimmune diseases in females.

Utility of magnetic resonance imaging in the evaluation of patients with inflammatory myopathies.

Magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (P-31 MRS) provide unique, quantitative data that cannot be obtained from routine laboratory tests. MRI is the method of choice for imaging of muscle abnormalities. It is also a very sensitive technique for localizing nonhomogeneous inflammation in inflammatory myopathies such as dermatomyositis, juvenile dermatomyositis, amyopathic dermatomyositis, polymyositis, and inclusion body myositis. During treatment of inflammatory myopathies, the extent and severity of inflammation may decrease at varying rates, but weakness and fatigue remain serious clinical problems. The metabolic abnormalities detected with P-31 MRS are more persistent and can be used for objective patient evaluation after the disappearance of inflammation and normalization of serum levels of muscle enzymes. With P-31 MRS, biochemical defects are quantitated, including low levels of ATP and phosphocreatine (PCr) and elevated concentrations of ADP and inorganic phosphate (Pi), which may all be related to weakness and fatigue. Thus, MRI and P-31 MRS are useful in assessing the status of patients with inflammatory myopathies during treatment with prednisone and immunosuppressive drugs.