The natural history of nonalcoholic fatty liver disease: a population-based cohort study

BACKGROUND & AIMS: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver-related morbidity among community-based NAFLD patients. METHODS: Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. RESULTS: Mean (SD) age at diagnosis was 49 (15) years; 231 (49%) were male. Mean follow-up was 7.6 (4.0) years (range, 0.1-23.5) culminating in 3192 person-years follow-up. Overall, 53 of 420 (12.6%) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003-1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7-2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3-5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2-7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7%) subjects. Twenty-one (5%) patients were diagnosed with cirrhosis, and 13 (3.1%) developed liver-related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. CONCLUSIONS: Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver-related death is a leading cause of mortality, although the absolute risk is low.     

Predictors of overall quality of care provided to vulnerable older people

OBJECTIVES: Prior research shows that the quality of care provided to vulnerable older persons is suboptimal, but little is known about the factors associated with care quality for this group. In this study, the influences of clinical conditions, types of care processes, and sociodemographic characteristics on the quality of care received by vulnerable older people were evaluated. DESIGN: Observational cohort study. SETTING: Two senior managed care plans. PARTICIPANTS: Three hundred sixty-two community-dwelling patients aged 65 and older identified as vulnerable by the Vulnerable Elder Survey (VES-13). MEASUREMENTS: Outcome variable: patients' observed-minus-expected overall quality score. Predictor variables: types of care processes, types and number of clinical conditions, sex, age, VES-13 score (composite score of function and self-rated health), income, education, mental health status, and number of quality indicators triggered. RESULTS: Patients whose conditions required more history-taking, counseling, and medication-prescribing care processes and patients with diabetes mellitus received lower-than-expected quality of care. A greater number of comorbid conditions was associated with higher-than-expected quality of care. Age, sex, VES-13 score, and other sociodemographic variables were not associated with quality of care. CONCLUSION: Complexity, vulnerability, and age do not predispose older persons to receive poorer-quality care. In contrast, older patients whose care requires time-consuming processes such as history taking and counseling are at risk for worse quality of care and should be a target for intervention to improve care.     

Phenotype variation in C282Y homozygotes for the hemochromatosis gene.

BACKGROUND & AIMS: Typical hemochromatosis patients are homozygous for the C282Y mutation of the HFE gene. However, approximately 50% of women and 20% of men do not have an increase in serum ferritin level. This study assessed factors, genetic and otherwise, that may modify biochemical expression in C282Y homozygotes. METHODS: Hemochromatosis families that each had at least 2 untreated C282Y homozygotes were included. Nonexpressors were defined as having a ferritin level less than 300 microg/L for a male and a ferritin level less than 200 microg/L for a female. A multivariate linear stepwise regression analysis was performed to assess the contribution of sex, age, and the presence of a nonexpressor in the family on serum ferritin level. Heritability calculations were performed using variance component analysis. RESULTS: Fifty-three pedigrees consisting of 148 C282Y homozygotes (92 males, 56 females) were identified. Twenty-nine homozygotes were nonexpressors (19.6%), of which 11 of 29 were male (37.9%) (P=.0054). Based on multivariate analysis, highly significant associations with increased ferritin levels in C282Y homozygotes were male sex (P=.00005), increasing age (P=.009), and absence of a nonexpressor in the family (P=.01). Variance component modeling using age, sex, and C282Y genotype as covariates in 39 pedigrees (n=296) showed a residual heritability for serum ferritin of .35+/-.10 (P<.001). CONCLUSIONS: These findings suggest that male sex is the major clinical factor associated with an increased serum ferritin level in hemochromatosis. In addition, these results support the hypothesis that other genes contribute to the variance in serum ferritin concentration among C282Y homozygotes.     

Aging and heart failure--similar syndromes of exercise intolerance? Implications for exercise-based interventions

A classic hallmark of chronic heart failure (CHF) is exercise intolerance; however, the extent of exercise limitation is not correlated with the degree of left ventricular dysfunction. Over the past 2 decades it has become more and more evident that peripheral factors, such as skeletal muscle dysfunction, ventilatory abnormalities, and endothelial dysfunction, contribute the greater part to the limitation of exercise capacity. The molecular and pathophysiological changes observed in these organ systems are not always specific to the underlying CHF but rather represent a common pathway that is activated in several chronic disease processes, including severe chronic obstructive pulmonary disease, cancer, and in the normal aging process. A major contributing factor for skeletal muscle catabolism (i.e. elevated cytokine expression in the skeletal muscle) can be found in both normal healthy aging and in heart failure patients. It is reasonable to assume that the overlap of aging and CHF-associated changes in the skeletal muscle partially explains the disabling consequences of the CHF syndrome among elderly patients (nearly 80% of all patients hospitalized for CHF are >65 years old). Peripheral alterations in CHF are often not adequately treated in routine clinical care since standard pharmacological therapy is still focused on the cardiac function and neurohormonal alteration. Exercise training is a guideline-oriented adjuvant therapy with well-documented beneficial effects on exercise tolerance, skeletal muscle function, endothelial function, and respiration. In this review, the effects of exercise in aging and in CHF are compared and the parallel mechanisms are explored.     

Clinical results of a novel wide beam reconstruction method for shortening scan time of Tc-99m cardiac SPECT perfusion studies.

BACKGROUND: Newly developed reconstruction algorithms enable the acquisition of images at half of the scan time while maintaining image quality. The purpose of this investigation was to evaluate a novel wide beam reconstruction (WBR) method developed by UltraSPECT for decreasing scan times and to compare it with filtered backprojection (FBP), which is the technique routinely used. METHODS AND RESULTS: Phantom and clinical studies were performed. Hot and cold sphere and cardiac phantom acquisitions were reconstructed via WBR, FBP, and ordered-subsets expectation maximization. Fifty patients were prospectively studied by use of both a standard and a short protocol. The short protocol was performed first on 29 of 50 patients via 8-frame gated technetium 99m stress single photon emission computed tomography and low-energy high-resolution collimators. Stress Tc-99m studies (30-45 mCi) were scanned for 20 seconds per frame. For the short protocol, all parameters remained constant except for the time per frame, which was reduced by 50% on Tc-99m studies. All resting Tc-99m scans (36/50 patients) were processed with FBP for the standard full-scan time studies and with WBR for the short scan studies. The images were interpreted by use of a 17-segment model and 5-degree severity score, and the perfusion and functional variables were determined. Distributions including mean, median, and interquartile ranges were examined for all variables. The differences (FBP - WBR) were computed for all variables and were examined by use of nonparametric signed rank tests to determine whether the median difference was 0. The absolute value of the difference was also examined. Spearman rank-order correlation, a nonparametric measure of association, was used for the 2 methods to determine significant correlations between variables. The hot and cold sphere phantom studies demonstrated that WBR had improved contrast recovery and slightly better background uniformity than did the ordered-subsets expectation maximization. The cardiac phantom studies performed with attenuating medium and background activity showed that the half-scan time images processed with WBR had better contrast recovery and background uniformity than did the full-scan time FBP reconstruction. In the clinical studies, highly significant correlations were observed between WBR and FBP for functional as well as perfusion variables (P < .0001). The summed stress score, summed rest scores, and summed difference score were not statistically different for FBP and WBR (P > .05). Left ventricular volumes had a high correlation coefficient but were significantly larger with FBP than with WBR. CONCLUSION: Our study results suggest that cardiac single photon emission computed tomography perfusion studies may be performed with the WBR algorithm using half of the scan time without compromising qualitative or quantitative imaging results.     

A review of clinical upper limb assessments within the framework of the WHO ICF

This paper is intended to provide a practical overview for clinicians and researchers involved in assessing upper limb function. It considers 25 upper limb assessments used in musculoskeletal care and presents a simple, straightforward comparative review of each. The World Health Organization International Classification on Functioning, Disability and Health (WHO ICF) is used to provide a relative summary of purpose between each assessment. Measurement properties of each assessment are provided, considering the type of data generated, availability of reliability estimates and normative data for the assessment.     

Punctuated evolution of mitochondrial gene content: high and variable rates of mitochondrial gene loss and transfer to the nucleus during angiosperm evolution

To study the tempo and pattern of mitochondrial gene loss in plants, DNAs from 280 genera of flowering plants were surveyed for the presence or absence of 40 mitochondrial protein genes by Southern blot hybridization. All 14 ribosomal protein genes and both sdh genes have been lost from the mitochondrial genome many times (6 to 42) during angiosperm evolution, whereas only two losses were detected among the other 24 genes. The gene losses have a very patchy phylogenetic distribution, with periods of stasis followed by bursts of loss in certain lineages. Most of the oldest groups of angiosperms are still mired in a prolonged stasis in mitochondrial gene content, containing nearly the same set of genes as their algal ancestors more than a billion years ago. In sharp contrast, other plants have rapidly lost many or all of their 16 mitochondrial ribosomal protein and sdh genes, thereby converging on a reduced gene content more like that of an animal or fungus than a typical plant. In these and many lineages with more modest numbers of losses, the rate of ribosomal protein and sdh gene loss exceeds, sometimes greatly, the rate of mitochondrial synonymous substitutions. Most of these mitochondrial gene losses are probably the consequence of gene transfer to the nucleus; thus, rates of functional gene transfer also may vary dramatically in angiosperms.     

The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease

BACKGROUND & AIMS: Celiac disease and hereditary hemochromatosis are common HLA-defined conditions in northwestern Europe. We sought to determine whether there is a genetic relationship between the 2 diseases and if hemochromatosis susceptibility gene (HFE) mutations are protective against iron deficiency in celiac disease. METHODS: Polymerase chain reaction amplification using sequence-specific primers capable of identifying the 2 HFE gene mutations (H63D and C282Y) and the HLA class I and II alleles was used to type 145 white patients with celiac disease and 187 matched controls. Hemoglobin and fasting serum iron levels in celiac patients were measured at diagnosis. RESULTS: HFE gene mutations, H63D or C282Y, were identified in 70 celiac patients (48.3%) and 61 controls (32.6%) (P = 0.004). The C282Y mutation was associated with HLA-A*03 and B*07 alleles in controls and with A*01, A*03, B*08, and DRB1*0301 alleles in celiac patients; the H63D mutation was associated with HLA-A*25 and DRB1*03 alleles in controls and A*29 and DRB1*03 alleles in celiac patients. At diagnosis, celiac patients with the C282Y mutation had higher mean hemoglobin and fasting serum iron levels compared with the HFE wild type (P = 0.0002 and 0.006, respectively). This was not observed with the H63D mutation. CONCLUSIONS: In celiac disease, HFE gene mutations are common and are in linkage disequilibrium with different HLA alleles compared with controls. A disease-specific haplotype that carries C282Y and DQB1*02 is suggested. We propose that HFE gene mutations provide a survival advantage by ameliorating the iron deficiency seen in celiac patients.     

Assessing periarticular bone mineral density in patients with early psoriatic arthritis or rheumatoid arthritis

BACKGROUND: Periarticular osteoporosis is an early finding in the hands of patients with rheumatoid arthritis (RA), due to release of bone resorbing cytokines from the inflamed synovium. There has been disagreement as to whether periarticular bone loss occurs in psoriatic arthritis (PsA). Bone mineral density (BMD) can now be measured accurately using dual energy x ray absorptiometry (DEXA). Recently, DEXA has been used to measure periarticular BMD at predefined regions of interest (ROIs) around the joints. OBJECTIVES: Firstly, to compare periarticular BMD around the finger joints of patients with early RA or PsA. Secondly, to determine whether periarticular bone loss is related to joint inflammation and radiological erosions in RA and PsA. METHODS: Seventeen patients with RA and 15 with PsA were recruited, all with disease duration of less than five years. All finger joints were examined by one person for swelling, or tenderness, or both. Hand radiographs were scored for the presence of erosions. Periarticular BMD was measured at 10 predetermined ROIs using a Hologic QDA-4500A fan-beam densitometer. RESULTS: Patients with PsA were less likely to be positive for rheumatoid factor (RF) (13% v 94%) and more likely to be men (60% v 23%) than patients with RA. There were no other clinical differences between patients with RA or PsA. Patients with RA had significantly lower BMD at each of the ROIs than those with PsA (p<0.05). However, these differences disappeared after adjusting for age and sex. Among patients with RA, those with a higher total number of swollen and/or tender hand joints had significantly lower periarticular BMD at the metocarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. No such association was found for patients with PsA. CONCLUSIONS: In early disease, periarticular bone loss occurred both in patients with RA and those with PsA. Among patients with RA, periarticular osteoporosis was related to measures of joint inflammation. There was no association between joint inflammation and periarticular bone loss in patients with PsA, which lends support to the hypothesis that the primary site of inflammation in PsA is extrasynovial.