Background Obesity is increasing in prevalence and is a major contributor to worldwide morbidity. One consequence of obesity might be an increased risk for periodontal disease, although periodontal inflammation might, in turn, exacerbate the metabolic syndrome, of which obesity is one component. This review aims to systematically compile the evidence of an obesity–periodontal disease relationship from epidemiologic studies and to derive a quantitative summary of the association between these disease states. Methods Systematic searches of the MEDLINE, SCOPUS, BIOSIS, LILACS, Cochrane Library, and Brazilian Bibliography of Dentistry databases were conducted with the results and characteristics of relevant studies abstracted to standardized forms. A meta-analysis was performed to obtain a summary measure of association. Results The electronic search identified 554 unique citations, and 70 studies met a priori inclusion criteria, representing 57 independent populations. Nearly all studies matching inclusion criteria were cross-sectional in design with the results of 41 studies suggesting a positive association. The fixed-effects summary odds ratio was 1.35 (Shore-corrected 95% confidence interval: 1.23 to 1.47), with some evidence of a stronger association found among younger adults, women, and non-smokers. Additional summary estimates suggested a greater mean clinical attachment loss among obese individuals, a higher mean body mass index (BMI) among periodontal patients, and a trend of increasing odds of prevalent periodontal disease with increasing BMI. Although these results are highly unlikely to be chance findings, unmeasured confounding had a credible but unknown influence on these estimates. Conclusions This positive association was consistent and coherent with a biologically plausible role for obesity in the development of periodontal disease. However, with few quality longitudinal studies, there is an inability to distinguish the temporal ordering of events, thus limiting the evidence that obesity is a risk factor for periodontal disease or that periodontitis might increase the risk of weight gain. In clinical practice, a higher prevalence of periodontal disease should be expected among obese adults.

We performed a cross-sectional study of newly diagnosed cases of nonalcoholic fatty liver disease (NAFLD) identified between December 1998 and December 2000 in the Chronic Liver Disease Surveillance Study. We compared the demographic and clinical features of NAFLD in a racially diverse representative U.S. population (Alameda County, CA). Diagnostic criteria for probable NAFLD were persistent unexplained elevation of serum aminotransferase levels, radiology (ultrasound or computed tomography scan) consistent with fatty liver, and/or two or more of the following: (i) body mass index of 28 kg/m 2 or more, (ii) type 2 diabetes, or (iii) hyperlipidemia, in the absence of significant alcohol use. Definite NAFLD cases required histological confirmation. Of the 742 persons with newly diagnosed chronic liver disease, 159 (21.4%) had definite or probable NAFLD. The majority were nonwhite: Hispanics (28%), Asians (18%), African Americans (3%), and other race(s) (6%). African Americans with NAFLD were significantly older than other racial or ethnic groups (P < .001), and in Asians, NAFLD was 3.5 times more common in males than in females (P ‫؍‬ .016). Clinical correlates of NAFLD (obesity, hyperlipidemia, diabetes) were similar among racial and ethnic groups, except that body mass index was lower in Asians compared with other groups (P < .001). Compared with the base population (Kaiser Permanente members), Hispanics with NAFLD were overrepresented (28% vs. 10%) and whites were underrepresented (45% vs. 59%). In conclusion, these racial and gender variations may reflect differences in genetic susceptibility to visceral adiposity, including hepatic involvement, and may have implications for the evaluation of persons with the metabolic syndrome. Clinicians need to be aware of the variable presentations of NAFLD in different racial and ethnic groups. (HEPATOLOGY 2005;41:372-379.)

In the absence of surrogate markers, the evaluation of suspected nonalcoholic fatty liver disease (NAFLD) is highly dependent on histological examination. The extent of sampling variability affecting the reliability of a single liver biopsy in patients with suspected NAFLD is poorly characterized. This prospective study aimed to correlate precise histological findings in paired biopsies-right and left lobe-in the diagnosis of NAFLD in morbidly obese subjects undergoing bariatric surgery employing both Brunt and Matteoni classifications and the NAFLD Activity Score (NAS). We also aimed to determine whether the composite histopathological findings of the two biopsies would improve diagnostic accuracy. Consecutive subjects had an intraoperative biopsy from both right and left lobes, evaluated and scored in a blinded manner. Intraobserver agreement was also assessed. Kappa coefficients of agreement were calculated. Forty-one subjects had acceptable biopsies. Agreement for steatosis was excellent and moderate for fibrosis. Concordance was only fair for most features of necroinflammation. Intraobserver agreement was only moderate for lobular inflammation. Excellent agreement was seen for the diagnosis of NASH using Brunt criteria and good agreement when using Matteoni and NAS scoring systems. Composite biopsy data particularly improved identification of hepatocyte ballooning. The diagnostic accuracy also improved substantially when composite features were compared with single-sided biopsy features, especially for the Matteoni and NAS scoring systems. In conclusion, significant sampling variability occurs in NAFLD, particularly for features of necroinflammation. This should be factored into the design of clinical trials and studies of the natural history of the disease.

High-risk sexual or iatrogenic exposures may be important contemporary risk factors for HCV infection. The spontaneous viral clearance rate (18%) in this contemporary study was similar to that reported for past studies of transfusion-associated HCV infection. Women were more likely to clear acute HCV infection than men.

To identify molecular and cellular mechanisms that determine when bone forms, and to elucidate the role played by osteogenic mesenchyme, we employed an avian chimeric system that draws upon the divergent embryonic maturation rates of quail and duck. Pre-migratory neural crest mesenchyme destined to form bone in the mandible was transplanted from quail to duck. In resulting chimeras, quail donor mesenchyme established significantly faster molecular and histological programs for osteogenesis within the relatively slower-progressing duck host environment. To understand this phenotype, we assayed for changes in the timing of epithelial-mesenchymal interactions required for bone formation and found that such interactions were accelerated in chimeras. In situ hybridization analyses uncovered donor-dependent changes in the spatiotemporal expression of genes, including the osteoinductive growth factor Bmp4. Mesenchymal expression of Bmp4 correlated with an ability of quail donor cells to form bone precociously without duck host epithelium, and also relied upon epithelial interactions until mesenchyme could form bone independently. Treating control mandibles with exogenous BMP4 recapitulated the capacity of chimeras to express molecular mediators of osteogenesis prematurely and led to the early differentiation of bone. Inhibiting BMP signaling delayed bone formation in a stage-dependent manner that was accelerated in chimeras. Thus, mandibular mesenchyme dictates when bone forms by temporally regulating its interactions with epithelium and its own expression of Bmp4. Our findings offer a developmental mechanism to explain how neural crest-derived mesenchyme and BMP signaling underlie the evolution of speciesspecific skeletal morphology.

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In patients with GI symptoms associated with systemic sclerosis and related disorders, the amplitude and frequency of intestinal contractions are typically <10 mm Hg and <2/min. Antral amplitude is low (<40 mm Hg) when antral hypomotility is observed.

Hepatitis C virus (HCV)-related liver failure is the leading indication for liver transplantation worldwide. After transplantation, virological recurrence is the rule, but the spectrum of histological injury is wide, ranging from the development of allograft cirrhosis within a few years to minimal hepatitis despite long-term follow-up. The immunological correlates of this variable natural history are poorly understood. Here, we studied the kinetics of the cellular immune responses, viral replication, and allograft histology in 24 patients who had undergone liver transplantation for HCV-related liver failure. Using direct ex vivo methodologies (i.e., interferon-gamma ELISPOT and major histocompatibility complex class I-peptide tetrameric complexes), we found that patients who experienced viral eradication after antiviral therapy showed restoration of HCV-specific T-cell responses, whereas patients with progressive HCV recurrence that failed to respond to therapy showed declining frequencies of these viral-specific effector cells. The cytotoxic T lymphocytes that peripherally reconstituted after transplantation were clonotypically identical to those present within the recipient explant liver, defined at the level of the T-cell receptor beta chain (one epitope/one clone). Moreover, the subset of patients who spontaneously demonstrated minimal histologic recurrence had more vigorous CD4 ؉ T-cell responses in the first 3 months, particularly targeting nonstructural proteins. We provide evidence that T-cell responses emerge after liver transplantation, and their presence correlates with improved histological and clinical outcomes. In conclusion, these results may help identify patients more likely to develop severe HCV recurrence and therefore benefit from current antiviral therapy, as well as provide a rationale for the future use of novel immunotherapeutic approaches. H epatitis C virus (HCV) infection is characterized by the high likelihood of chronicity after acute infection and significant risk of disease progression to cirrhosis and liver failure. Immune responses appear to be crucial in the control of infection, and patients with self-limited courses of acute HCV demonstrate coordinated activation of viral-specific CD4 ϩ and CD8 ϩ T cells that produce type 1 cytokines such as interferon gamma (IFN-␥) and tumor necrosis factor-␣. 1 Moreover, these T-cell responses can be maintained for decades after recovery. Cellular immune responses also may offer varying degrees of protection against viral replication and tissue damage in persistent infection. 2 For example, an inverse correlation between levels of HCV-specific cytotoxic T lymphocytes, and viral load has been observed in humans and chimpanzees, 3-5 and HCV-related pathology is more prevalent in the setting of human immunodeficiency virus immune suppression. 2 HCV-related liver failure is the single most common indication for orthotopic liver transplantation (OLT) worldwide. 6 Recurrent HCV infection, as defined by viremia after transplantation, is nearly univ...