Morphopathological study in age related macular degeneration

The aim of this paper is to study the morphopathological changes manifested in age-related macular degeneration. MATERIAL AND METHOD: The researched histopathological material consisted in two eye balls enucleated because of irreversible eye diseases from aged persons suffering from age-related macular degeneration. The method applied for processing the material was inclusion in paraffin, followed by usual coloration with hematoxylin-eosin. RESULTS AND CONCLUSIONS: The established changes (hard drusen, soft drusen, calcified drusen, changes of Bruch's membrane, subretinal neovascularization, serous retinal pigment epithelial detachment, disciform degeneration) prove the importance of Bruch's membrane in the pathogenesis of age-related macular degeneration.     

Vascular calcifications in chronic kidney disease--clinical management

Chronic kidney disease (CKD) patients could present various types of calcifications causing different pathological conditions that would contribute to the renal disease progression and high risk of mortality. Extra-skeletal calcifications represent a common consequence of mineral bone disorders in CKD patients. Vascular calcifications represent a complex systemic manifestation caused by phospho-calcium homeostasis disorders, by imbalance among promoters and inhibitors of calcification and the presence of various arterial diseases and other risk factors. Consequently, vascular calcification can be considered an active pathological process that resembles osteogenesis. Therefore, before starting a suitable therapy for the prevention or delay of vascular calcifications, our recommendations are: to perform lateral abdominal radiography or CT-based techniques in CKD stages 3-5 patients for an early vascular calcification detection, to assess thoroughly patients presenting hyperphosphatemia, hyperparathyroidism, vitamin D deficiency and to understand clearly the pathophysiology of arterial calcification and calciphylaxis.     

Inflammatory reaction in chronic periodontopathies in patients with diabetes mellitus. Histological and immunohistochemical study

Chronic periodontopathies and diabetes mellitus are two clinical entities, which reciprocally condition one another. The periodontal disease is considered a major complication, which induces an unfavorable evolution of diabetes mellitus. Diabetes mellitus is an endocrine disease which favors the occurrence of periodontopathy through gum's microvascular disorders, the selection and development of an aggressive bacterial plaque and through an exaggerate inflammatory response to the microflora within the oral cavity. Both diabetes mellitus and periodontal disease have an increasing incidence in the whole world. Development of periodontopathy is related to the aggression of bacterial flora in dental plaque, flora that is influenced on its turn by the evolution of diabetes mellitus. In our study, we have evaluated the inflammatory reaction in periodontium in patients with slowly and progressive periodontitis in patients with diabetes mellitus who had diabetes longer than five years. It has been found that all patients presented a chronic inflammatory infiltrate, abundant, with round mononuclear cells of lymphocyte, plasma cells and macrophage type, with non-homogenous arrangement, more intensely where the covering epithelium presented erosions or necrotic areas. Out of the immunity system cells, the most numerous where of T-lymphocytes type.     

Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.     

Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms

In a previous study, we identified somatic mutations of SF3B1, a gene encoding a core component of RNA splicing machinery, in patients with myelodysplastic syndrome (MDS). Here, we define the clinical significance of these mutations in MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). The coding exons of SF3B1 were screened using massively parallel pyrosequencing in patients with MDS, MDS/MPN, or acute myeloid leukemia (AML) evolving from MDS. Somatic mutations of SF3B1 were found in 150 of 533 (28.1%) patients with MDS, 16 of 83 (19.3%) with MDS/MPN, and 2 of 38 (5.3%) with AML. There was a significant association of SF3B1 mutations with the presence of ring sideroblasts (P < .001) and of mutant allele burden with their proportion (P = .002). The mutant gene had a positive predictive value for ring sideroblasts of 97.7% (95% confidence interval, 93.5%-99.5%). In multivariate analysis including established risk factors, SF3B1 mutations were found to be independently associated with better overall survival (hazard ratio = 0.15, P = .025) and lower risk of evolution into AML (hazard ratio = 0.33, P = .049). The close association between SF3B1 mutations and disease phenotype with ring sideroblasts across MDS and MDS/MPN is consistent with a causal relationship. Furthermore, SF3B1 mutations are independent predictors of favorable clinical outcome, and their incorporation into stratification systems might improve risk assessment in MDS.     

"Immuknow" to measurement of cell-mediated immunity in renal transplant recipients undergoing short-term evaluation

The aim of this preliminary, observational study was to evaluate the value of ImmuKnow (IK), a new tool to measure the net state of immunefunction among renal transplant recipients, in correlation with clinical and laboratory data among unselected renal transplant recipients. Forty-nine recipients of mean age of 51 years were enrolled and followed for 1 year after transplantation. All subjects received the same immunosuppressive strategy with basiliximab induction and tacrolimus, mycophenolate mofetil and steroid maintenance therapy. Samples for IK were collected before transplantation as well as at 7, 14, 21 and 42 days and after 3, 6, and 12 months. There were 54 samples with IK <225 ng/mL, 201 samples with normal IK values, and 135 samples with >525 ng/mL. We divided recipients into 3 groups with respect to their basal IK values: Group 1 (Gr1; IK <225 ng/mL); Group 2 (Gr2; normal values of IK between 226 and 524 ng/mL); and Group 3 (Gr3; IK >525 ng/mL). At 1 year, we observed a significant difference among IK values at the start and the end of the study: Gr1 vs Gr2, P < .0001; Gr2 vs Gr3, P < .06 and Gr 1 vs Gr 3, P < .01). We observed reduced IK values to predict an increased risk of infection, particularly with cytomegalovirus (CMV) replication while higher IK value did not correlate with an increased risk of acute rejection episodes. Reduction of serum creatine levels occurred within 1 year in all groups (P < .005), but there was a significant difference between Gr 2 versus Grs 1 and 3 (P < .0001 and P < .0005, respectively). There findings suggested that more stable IK values were associated with clinical quiescence and laboratory stability. In conclusion, our preliminary analysis showed a beneficial capacity of this assay to represent the global depression of the immune system. We noted that reduced IK values, as a sign of excessive immunosuppressive therapy, were associated with an increased risk of infection. We did not confirm the predictive value of higher IK values for an increased risk of an acute rejection episode.     

Change in Predicted 10-Year Cardiovascular Risk Following Roux-en-Y Gastric Bypass Surgery: Who Benefits?

Background  

The risk of developing cardiovascular disease is higher in obese than in non-obese individuals. Surgery for obesity is effective in reducing weight and resolution of diabetes, hypertension, and dyslipidemia. Our aim was to assess the estimated 10-year cardiovascular risk of obese patients before and after treatment of obesity with a gastric bypass.     

Ovarian cancer

Ovarian cancer accounts for 4% of all cancers in women and is the leading cause of death from gynaecologic malignancies. Because early-stage ovarian cancer is generally asymptomatic, approximately 75% of women present with advanced disease at diagnosis. Survival is highly dependent on stage of disease: 5-year survival in patients with early-stage is 80-90% compared to 25% for patients with advanced-stage disease. For all patients, a comprehensive surgical staging should be performed to obtain the histological confirmation of diagnosis and to evaluate the extent of disease. Patients with early-stage should both be optimally staged and be treated with adjuvant platinum-based chemotherapy if they have a medium or high-risk tumour. For advanced disease the currently recommended management is primary cytoreductive surgery followed by platinum-paclitaxel combination chemotherapy. Appropriate salvage therapy is based on the timing and nature of recurrence and the extent of prior chemotherapy. Surgical resection should be considered in patients with long-term remission, especially in those with isolated recurrences and good performance status. Platinum-based combination represents the standard second-line chemotherapy in patients with platinum-sensitive relapsed ovarian cancer. Salvage chemotherapy in platinum-refractory patients usually results in low response rates and short survival.     

The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease

Background It has recently been demonstrated that the Wilson disease (WD) protein directly interacts with the human homolog of the MURR1 protein in vitro and in vivo, and that this interaction is specific for the copper transporter. The aim of the present study was to clarify the role of MURR1 in the pathogenesis of WD as well as in other WD-like disorders of hepatic copper metabolism of unknown origin. Methods Using the single-strand conformation polymorphism (SSCP) method followed by sequencing, we analyzed the 5′ untranslated region (UTR) and three exons of the MURR1 gene in three groups of patients: 19 wd patients in whom no mutations were detected in the ATP7B gene, 53 wd patients in whom only one mutation in the ATP7B gene was found, and 34 patients in whom clinical and laboratory data suggested a WD-like disorder of hepatic copper metabolism of unknown origin. Results We  detected in these patients six rare nucleotide substitutions, namely one splice-site consensus sequence and one missense and four silent nucleotide substitutions. All substitutions except one were found in the heterozygous state. No difference in the frequencies of the various substitutions was observed between patients and controls. Conclusions These data suggest that the MURR1 gene and its protein product are unlikely to play a primary role in the pathogenesis of Wilson disease. More extensive studies with larger numbers of clinically homogeneous patients should be carried out to establish whether nucleotide alterations in the MURR1 gene may have a role in causing WD or WD-like disorders or act as modifying factors in the phenotype variability in WD.