Is obesity an inflammatory disease?

BACKGROUND: Most obese individuals have elevated concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), markers of inflammation closely associated with diabetes, hypertension, and stroke. HYPOTHESIS: Obesity is a low-grade inflammatory disease, and Roux-en-Y gastric bypass (RYGB) reduces biochemical markers of inflammation and modifies gene expression in hypothalamic food intake/energy-related nuclei and subcutaneous abdominal fat (SAF). METHODS: Obesity was induced in 24 3-week-old Sprague Dawley pups fed a high-energy diet (HED). Three groups (n = 8/group) were studied: RYGB, sham-operated pair-fed, and sham-operated ad libitum HED. Controls were nonobese rats fed chow (n = 6). Rats were killed 10 days after operation, and blood was collected to measure corticosterone and SAF and mesenteric fat to measure IL-6, TNF-alpha, and corticosterone. Total mRNA from arcuate nucleus and SAF purified for gene expression profiling. Data were analyzed with analysis of variance, Mann-Whitney test, and t test. RESULTS: Before operation, the body weight of the obese groups was 493 +/- 7 g and control = 394 +/- 12g. The 10-day postoperative weight was RYGB = 417 +/- 21 g, pair-fed = 436 +/- 14 g, and ad libitum HED = 484 +/- 15 g. Mesenteric and SAF weight decreased in RYGB. Mesenteric/SAF ratio of IL-6, TNF-alpha, corticosterone, and gene profiling showed decrease of inflammation after RYGB. CONCLUSIONS: Gastric bypass reduces biochemical markers of inflammation, suggesting that obesity is an inflammatory condition.     

Ischemic acute renal failure: an inflammatory disease?

Inflammation plays a major role in the pathophysiology of acute renal failure resulting from ischemia. In this review, we discuss the contribution of endothelial and epithelial cells and leukocytes to this inflammatory response. The roles of cytokines/chemokines in the injury and recovery phase are reviewed. The ability of the mouse kidney to be protected by prior exposure to ischemia or urinary tract obstruction is discussed as a potential model to emulate as we search for pharmacologic agents that will serve to protect the kidney against injury. Understanding the inflammatory response prevalent in ischemic kidney injury will facilitate identification of molecular targets for therapeutic intervention.     

Laparoscopic surgery for inflammatory bowel disease: does weight matter?

Background  

Recent studies have shown improved outcomes after laparoscopic colorectal surgery compared with laparotomy for surgery for both benign and malignant colorectal diseases, including inflammatory bowel disease (IBD). This study was designed to evaluate the results of laparoscopic colorectal resections in normal weight patients compared with overweight and obese patients with IBD.     

Evaluating inflammatory joint disease: how and when can autoantibodies help?

The diagnosis of inflammatory joint disease rests on a constellation of symptoms, signs, laboratory test results and, occasionally, histological findings. Classification criteria have been developed by national learned societies, international panels of experts or, more rarely, an expert working alone. These criteria are intended to provide a common language for therapeutic trials and international publications. Yet, they are often inappropriately used as diagnostic tools for the individual patient. Identification of an early seroimmunologic marker with high sensitivity and specificity for classifying patients with recent-onset joint disease is a daunting challenge. Test performance characteristics such as sensitivity, specificity, positive and negative predictive values, and the positive or negative likelihood ratio help to assess the diagnostic usefulness of a laboratory test in a specific situation. The difference between the pretest and posttest likelihoods of obtaining a positive or negative result measures the usefulness, or performance, of a laboratory test in a specific situation according to the prevalence of the disease. A higher positive likelihood ratio indicates a more useful test. In a patient with inflammatory joint disease, the diagnosis can be sought by assaying a limited number of autoantibodies according to a decision tree. Thus, IgM rheumatoid factors (latex test or ELISA) and antibodies to filaggrin or other citrullinated proteins (antikeratin antibodies by indirect immunofluorescent assay or anticyclic citrullinated peptides by ELISA) identify more than 70% of cases of early rheumatoid arthritis with greater than 98% specificity. If these markers are negative, testing for antinuclear antibodies by indirect immunofluorescent assay on HEp-2 cells identifies 99% of cases of lupus and progressive systemic sclerosis. Confirmation of the diagnosis can be obtained by characterizing the autoantibodies: thus, presence of antidouble-stranded DNA (dsDNA, by the Farr radioimmunoassay, indirect immunofluorescent assay on Crithidia luciliae, or ELISA (IgG)) or of antinucleosome antibodies (ELISA) indicates lupus, whereas anticentromere, antitopoisomerase I (Scl 70), and antinucleolar antibodies point to progressive systemic sclerosis. A positive test for antibodies to soluble nuclear antigens of the U1 RNP type suggests mixed connective tissue disease or lupus but may indicate scleroderma. Anti-Sm antibodies are found in fewer than 10% of lupus patients but are highly specific. Anti-SSA (Ro) and anti-SSB (La) suggest lupus or primary Sj?gren's syndrome. When tests are negative for ANA, several antibodies to cytoplasmic organelles are valuable diagnostic tools, such as anti-J01 for polymyositis syndromes and antiribosome antibodies for lupus, although their sensitivity is modest (20-25%). Finally antineutrophil cytoplasmic antibodies (ANCAs) ensure the diagnosis of small-vessel vasculitides, which often involve the lungs and kidneys. Thus, in diffuse Wegener's granulomatosis, ANCAs exhibiting the classic cytoplasmic pattern and corresponding by ELISA to anti-PR3 are found. In microscopic polyangiitis the ANCAs are peripheral and correspond by ELISA to antimyeloperoxidase antibodies. Tests for other antibodies are less often needed to evaluate inflammatory joint disease.     

Ultrasonography in inflammatory joint disease: why should rheumatologists pay attention?

During the last decade, articular ultrasonography (US) has been found effective in evaluating inflammatory, degenerative, and traumatic abnormalities of articular and periarticular tissues. In clinical practice, US used in combination with a thorough clinical evaluation can help rheumatologists to confirm or to refute diagnostic hypotheses. US is safer than computed tomography (CT), an advantage shared by magnetic resonance imaging (MRI). As compared to CT and MRI, US is less expensive; in addition, it can be performed immediately, for several joints, as often as needed. Furthermore, US allows dynamic studies. Several articles published in rheumatology journals emphasize the value of US in patients with musculoskeletal diseases. The present review article discusses the indications, efficacy, and limitations of articular US.     

Is inflammatory joint disease in HIV-infected patients a form of spondyloarthropathy?

In Congo-Brazzaville, the seroprevalence of HIV infection is in the range 7-8%, and AIDS is the leading cause of aseptic arthritis (60% of cases). PATIENTS, MATERIAL AND METHODS: The ESSG and Amor's criteria for spondyloarthropathy were evaluated in 83 patients with HIV infection admitted for aseptic arthritis to the rheumatology department of the Brazzaville teaching hospital, over an 8-year period. RESULTS: All 83 patients were CDC stage IV; 66 (80%) had polyarthritis and 17 (20%) oligoarthritis. A single patient met ESSG and Amor's criteria, with six points; one patient had five points and 15 had three points. The joint involvement was asymmetrical and nonerosive. Nonsteroidal antiinflammatory therapy ensured resolution of the manifestations within 4-8 weeks. The most common sites of involvement were the knees (84%), ankles (59%), and great toes (23%) at the lower limbs and the wrists (41%), elbows (29%), and metacarpophalangeal and interphalangeal joints (25%) at the upper limbs. CONCLUSION: Inflammatory arthritis in HIV patients does not meet ESSG or Amor's criteria for spondyloarthropathy.     

Renal impairment in patients with inflammatory bowel disease: association with aminosalicylate therapy?

BACKGROUND: In recent years, several case reports have been published suggesting an association between the use of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) and the development of chronic tubulo-interstitial nephritis. Apart from lesions associated to 5-ASA treatment, however, it is clear that IBD itself may also induce renal impairment, albeit the frequency is unknown. METHODS: During 1 year, all IBD patients seen at the outpatient clinic of 27 European centres of gastro-enterology were registered and screened for renal impairment controlling for a possible association with 5-ASA therapy. Patients were questioned about their medical and drug history and their IBD disease activity. Renal screening (calculated creatinine clearance) was performed at baseline, after 6 and 12 months. RESULTS: Included patients (n = 1,529) had a mean age of 39 (range 14-98), 56% had Crohn's disease, 42% ulcerative colitis and 2% indeterminate colitis. Half of the patients used 5-ASA during the study period. Decreased creatinine clearance was observed in 34 patients, among them 13 with chronic renal impairment. Comparing patients with and without renal impairment, no difference could be observed in 5-ASA consumption. In contrast, patients with renal impairment were significantly older, had a lower body mass index and showed a higher frequency of male sex, bowel resection and stoma. CONCLUSION: Although the association between 5-ASA therapy and chronic tubulo-interstitial nephritis is clearly described in several case reports, this prospective study came to the reassuring conclusion that renal impairment in IBD patients is not frequently observed and is rarely associated with 5-ASA therapy.     

Warthin's tumour in the parotid gland (an inflammatory or a neoplastic disease?)

Warthin's tumour has always been considered a peculiar neoplasm with specific anatomico-pathological characteristics. In this study we argue that it should not be considered a true neoplasm but simply an inflammatory process which is triggered by the indiscriminate use of tobacco and involves the parotid duct. In the 10 cases treated in our department, Warthin's tumour has predominantly affected males (9:1) and heavy smokers. Our treatment of choice has been enucleoresection. The results have been satisfactory, with no complications such as salivary fistula or permanent lesions of the facial nerve. In two subjects, treated by enucleoresection, there was a pleomorphic adenoma: in one on the same side as previous surgery performed two years earlier and, in the second, in the contralateral gland 4 years after surgery. Both patients, who underwent total parotidectomy, recovered perfectly without complications. Smoking appears to be involved in the development of Warthin's tumour and might be regarded as an inflammatory reaction to smoking or to ionising radiation. Ultrasound and FNAB are necessary for planning the correct surgical strategy, and enucleoresection, in our opinion, is the treatment of choice.     

Use of double-balloon enteroscopy in the management of patients with Crohn’s disease: feasibility and diagnostic yield in a high-volume centre for inflammatory bowel disease

Background  

Double-balloon enteroscopy (DBE) is theoretically useful in Crohn’s disease (CD) since it is potentially able to investigate the whole small intestine, but sparse data are available.     

Collapsing glomerulopathy: an inflammatory podocytopathy?

PURPOSE OF REVIEW: Collapsing glomerulopathy is a relatively new and debated podocytopathy. Among several conjectures, inflammatory injury orchestrated by podocytes is emerging to explain the pathogenesis of collapsing glomerulopathy. Here, we briefly summarize recent studies in support of this novel and intriguing hypothesis. RECENT FINDINGS: Immunohistochemical analyses of markers conventionally used to demarcate podocytes apart from parietal epithelium identified the parietal podocyte. MafB-deficient mice exhibited abnormal podocyte and macrophage differentiation, suggesting ancestral and functional overlap. These apparent developmental anomalies were detected in studies showing an admixture of hyperplastic podocytes with macrophage epitopes and hyperplastic parietal epithelium in pseudocrescents and in true crescents. Experimental antibody-mediated injury of podocytes could trigger capillary collapse and pseudocrescent formation marked by recruitment of epithelial cells from Bowman's capsule. In contrast, experimental stabilization of hypoxia-inducible factors within podocytes--a known inflammatory response by macrophages--could trigger podocyte proliferation and the formation of true necrotizing crescents. SUMMARY: Preliminary evidence suggests that visceral and parietal podocytes may become macrophage-like inflammatory mediators of proliferative epithelial injury within the glomerulus. This may manifest as collapsing glomerulopathy or crescentic glomerulonephritis--lesions that appear to be anatomically and pathogenically linked.     

Cardiac Behçet disease presenting as aortic valvulitis/aortitis or right heart inflammatory mass: a clinicopathologic study of 12 cases

Beh?et disease is an inflammatory disorder of unknown etiology showing diverse clinical presentations. Cardiac involvement is a critical problem that requires a timely diagnosis and management. However, clinicopathologic features have not been characterized clearly. Here, we present clinicopathologic characteristics of this uncommon disease. Patients included 8 males and 4 females, ranging from 24 to 52 years old. They were presented with abrupt heart failure and were mostly diagnosed as having cardiac Beh?et disease later in the course. Upon echocardiography, 8 patients showed severe aortic regurgitation with redundant prolapsing aortic cusps and 4 patients showed irregular mass lesions in the right ventricular cavity. No one had both lesions. The aortic root was also involved with aortic valvulitis, showing severe mixed acute and chronic inflammation of various stages. There were frequent microabscess and extensive endothelial loss with fibrinous deposit. The right heart lesions showed similar histopathologic features. Four patients who initially underwent simple aortic valve replacement developed serious postoperative complications requiring reoperations. No serious complications developed after the treatment was changed to a replacement of aortic root with extensive debridement and concomitant immunosuppressive therapy. Cardiac Beh?et disease is presented as aortic valvulitis/aortitis or inflammatory mass lesion. Characteristic echocardiographic and pathologic findings seem to be helpful for the timely diagnosis of this critical disease.