DENTAL CARIES AND PERIODONTAL DISORDERS IN CHRONIC LIVER DISEASE

Bacterial infections are frequent complications in patients with chronic liver disease (CLD). A potential source of infection may be dental foci. This study was carried out to assess the association of CLD with dental caries and periodontal disease. Dental caries and periodontal examinations were performed prospectively in patients with CLD (group A) and controls without any liver disease (group B). Similar examination was also carried out in alcoholics without liver disease (group C) as well as in cases with portal hypertension but no liver disease (group D) i.e. patients with Non Cirrhotic Portal Fibrosis and Extrahepatic portal obstruction. A total of 231 subjects (Group A:83, group B: 75, group C:46 and group D:27) were studied. Group A included 32 cases with chronic hepatitis B&C, 26 with alcoholic cirrhosis, 14 with postnecrotic cirrhosis, and 11 with cryptogenic cirrhosis. Measures of oral hygiene (p < 0.01), dental care (p < 0.001), and periodontal parameters were worse and the number of teeth requiring treatment (p < 0.05) was higher in alcoholics with or without cirrhosis than in healthy subjects and nonalcoholic patients with cirrhosis. Alcoholics had a lower, total number of teeth than patients without alcohol abuse and healthy controls (p < 0.01). The dental caries and periodontal status of patients with nonalcoholic cirrhosis did not differ significantly from group B. The severity and duration of liver disease had no influence on dental caries and periodontal disease. The presence of chronic alcohol abuse rather than cirrhosis or portal hypertension is a major predisposing factor for dental caries and periodontal diseases. In alcoholics, these diseases appear to be caused primarily by bad oral hygiene and poor dental care.KEY WORDS: Alcohol abuse, Chronic liver disease, Dental caries, Periodontal disease     

EAU Guidelines on Renal Cell Carcinoma: The 2010 Update

Context and objectives

The European Association of Urology Guideline Group for renal cell carcinoma (RCC) has prepared these guidelines to help clinicians assess the current evidence-based management of RCC and to incorporate the present recommendations into daily clinical practice.

Evidence acquisition

The recommendations provided in the current updated guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials.

Evidence synthesis

A number of recent prospective randomised studies concerning RCC are now available with a high level of evidence, whereas earlier publications were based on retrospective analyses, including some larger multicentre validation studies, meta-analyses, and well-designed controlled studies.

Conclusions

These guidelines contain information for the treatment of an individual patient according to a current standardised general approach. Updated recommendations concerning diagnosis, treatment, and follow-up can improve the clinical handling of patients with RCC.     

Ablation of the tumor suppressor histidine triad nucleotide binding protein 1 is protective against hepatic ischemia/reperfusion injury

The identification of cellular pathways capable of limiting ischemia/reperfusion (I/R) injury remains a frontier in medicine, and its clinical relevance is urgent. Histidine triad nucleotide binding protein 1 (HINT1) is a tumor suppressor that influences apoptosis. Because apoptotic pathways are a feature of I/R injury, we asked whether Hint1 influences hepatic I/R injury. Hint1(-/-) and C57BL/6 mice were subjected to 70% liver ischemia followed by reperfusion for 3 or 24 hours or to a sham operation. The serum aminotransferase levels, histological lesions, apoptosis, reactive oxygen species, and expression of B cell lymphoma 2-associated X protein (Bax), heme oxygenase 1 (HO-1), interleukin-6 (IL-6), IL-10, tumor necrosis factor-a, Src, nuclear factor kappa B (p65/RelA), and c-Jun were quantified. The responses to toll-like receptor ligands and nicotinamide adenine dinucleotide phosphate oxidase activity in Kupffer cells were compared in Hint1(-/-) mice and C57BL/6 mice. After I/R, the levels of serum aminotransferases, parenchymal necrosis, and hepatocellular apoptosis were significantly lower in Hint1(-/-) mice versus control mice. Furthermore, Bax expression decreased more than 2-fold in Hint1(-/-) mice, and the increases in reactive oxygen species and HO-1 expression that were evident in wild-type mice after I/R were absent in Hint1(-/-) mice. The phosphorylation of Src and the nuclear translocation of p65 were increased in Hint1(-/-) mice, whereas the nuclear expression of phosphorylated c-Jun was decreased. The levels of the protective cytokines IL-6 and IL-10 were increased in Hint1(-/-) mice. These effects increased survival after I/R in mice lacking Hint1. Hint1(-/-) Kupffer cells were less activated than control cells after stimulation with lipopolysaccharides. CONCLUSION: The Hint1 protein influences the course of I/R injury, and its ablation in Kupffer cells may limit the extent of the injury.     

Vaccines with the MF59 adjuvant do not stimulate antibody responses against squalene

Squalene is a naturally occurring oil which has been used in the development of vaccine adjuvants, such as the oil-in-water emulsion MF59. In past years, by use of noncontrolled and nonvalidated assays, a claim was made that antisqualene antibodies were detectable in the sera of individuals with the so-called Gulf War syndrome. Using a validated enzyme-linked immunosorbent assay for the quantitation of immunoglobulin G (IgG) and IgM antibodies against squalene, we demonstrated that antisqualene antibodies are frequently detectable at very low titers in the sera of subjects who were never immunized with vaccines containing squalene. More importantly, vaccination with a subunit influenza vaccine with the MF59 adjuvant neither induced antisqualene antibodies nor enhanced preexisting antisqualene antibody titers. In conclusion, antisqualene antibodies are not increased by immunization with vaccines with the MF59 adjuvant. These data extend the safety profile of the MF59 emulsion adjuvant.     

Temporal overexpression of IL‐22 and Reg3γ differentially impacts the severity of experimental autoimmune encephalomyelitis

IL‐22 is an alpha‐helical cytokine which belongs to the IL‐10 family of cytokines. IL‐22 is produced by RORγt+ innate and adaptive lymphocytes, including ILC3, γδ T, iNKT, Th17 and Th22 cells and some granulocytes. IL‐22 receptor is expressed primarily by non‐haematopoietic cells. IL‐22 is critical for barrier immunity at the mucosal surfaces in the steady state and during infection. Although IL‐22 knockout mice were previously shown to develop experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), how temporal IL‐22 manipulation in adult mice would affect EAE course has not been studied previously. In this study, we overexpressed IL‐22 via hydrodynamic gene delivery or blocked it via neutralizing antibodies in C57BL/6 mice to explore the therapeutic impact of IL‐22 modulation on the EAE course. IL‐22 overexpression significantly decreased EAE scores and demyelination, and reduced infiltration of IFN‐γ+IL‐17A+Th17 cells into the central nervous system (CNS). The neutralization of IL‐22 did not alter the EAE pathology significantly. We show that IL‐22‐mediated protection is independent of Reg3γ, an epithelial cell‐derived antimicrobial peptide induced by IL‐22. Thus, overexpression of Reg3γ significantly exacerbated EAE scores, demyelination and infiltration of IFN‐γ+IL‐17A+ and IL‐17A+GM‐CSF+Th17 cells to CNS. We also show that Reg3γ may inhibit IL‐2‐mediated STAT5 signalling and impair expansion of Treg cells in vivo and in vitro. Finally, Reg3γ overexpression dramatically impacted intestinal microbiota during EAE. Our results provide novel insight into the role of IL‐22 and IL‐22‐induced antimicrobial peptide Reg3γ in the pathogenesis of CNS inflammation in a murine model of MS.     

Renal small cell oncocytoma with pseudorosettes A histomorphologic, immunohistochemical, and molecular genetic study of 10 cases

A cohort of a heretofore not described rare subtype of renal oncocytoma, small cell oncocytoma with pseudorosettes is presented. Patients were 6 women and 4 men with ages ranging from 51 to 76 years. The tumors displayed areas composed of small cells ("oncoblasts") featuring scant cytoplasm and small, round monomorphic nuclei. The small cell areas constituted 15% to 60% of the total tumor volume (mean, 28.5%; median, 22.5%). No necrosis or mitotic activity was discerned. All tumors also contained areas composed of characteristic oncocytes comprising 40% to 85% of the total tumor volume. In all cases, a varying number of pseudorosettes were identified. The pseudorosettes were composed of small globules of (periodic acid-Schiff-positive) hyaline basal membrane-like material surrounded by small "oncoblastic" cells. The immunohistochemical profile was variable, including at least focal positivity for AE1-3 (10/10), cytokeratin 7 (7/10), epithelial membrane antigen (10/10), c-kit (6/10), antimitochondrial antigen (MIA;10/10), PAX-2 (9/10), AMACR (racemase;6/10), CD10 (5/10), parvalbumin (8/10), vimentin (6/10), claudin 7 (10/10), and claudin 8 (3/10). No immunoreactivity for carbonic anhydrase 9, HMB-45, S-100A1, and TFE3 was documented. We found no differences in the immunophenotype in the small cell oncocytes/oncoblasts that formed pseudorosettes and those that did not. However, there were differences in the immunohistochemical profile of classic oncocytes and small cell oncocytes/oncoblasts. Using array comparative genomic hybridization, no chromosomal changes were identified in any of the cases examined (n = 3). No numerical changes of chromosomes 7 and 17 were revealed on fluorescence in situ hybridization analysis (n = 3). In conclusion, we herein present the first study on small cell renal oncocytomas with formation of pseudorosettes. This is a rare subtype of oncocytoma, which may, especially on a core biopsy, present differential diagnostic difficulties. The immunohistochemical profile of these tumors is variable and differs in significant respects from that of conventional renal oncocytoma. Awareness of this entity and its immunohistochemical variability should help in distinguishing this rare tumor from malignant tumors with similar (small cell) histomorphologic features. All tumors behaved in a benign fashion during follow-up (mean, 3.1 years; median, 1 year).     

Entfernung von Verriegelungsnägeln an der oberen und unteren Extremität

BACKGROUND: Absolute indications for removing intramedullary locking nails (ILN) are undisputed, but there are also relative indications when implant removal might be discussed. The aim of our study was to evaluate complications of ILN removal in the upper and lower extremities. METHODS: Four hundred sixty (460) patients who underwent interlocking nail removal were reviewed regarding complications after removal of implants in the humerus, femur, or tibia. RESULTS: The most common complications were delayed wound healing and wound infections. For the humerus, the complication rate of implant removals due to absolute indication was 29%, and the rate for removals due to relative indication was 12%. In the forearm, no complications were seen. Patients who underwent ILN removal in the femur or tibia for absolute indication had a 21% complication rate; the complication rate in patients with relative indication was 10%. CONCLUSION: The complication rate of interlocking nail removal is too high to justify such a procedure without clear indication.