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Major Predisposing Factor (major + predisposing_factor)

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Medical Sciences	100%

Selected Abstracts

Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor loci

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2006
Mariska Hage
Abstract Barrett's esophagus (BE) is a major predisposing factor for the development of esophageal adenocarcinoma. Current strategies for treatment of BE, both dysplastic and nondysplastic, include photodynamic therapy (PDT) and argon plasma coagulation (APC). However, the effect of ablative therapy at the genetic level is unclear. We performed loss of heterozygosity (LOH) analysis of BE in baseline and follow-up biopsy specimens from 21 patients with BE (17 male, 4 female) treated with PDT and/or APC. At baseline, 14 patients had intestinal metaplasia without dysplasia (MET), 4 low-grade dysplasia (LGD) and 3 high-grade dysplasia (HGD). LOH was assessed using a panel of 9 polymorphic markers for evaluation of the P53 gene on 17p, P16 on 9p, DCC and SMAD4 on 18q and the APC gene on 5q. The tissue specimens obtained at baseline (t = 0) were analysed, as well as the first (t = 1; mean interval: 4 months) and last (t = 2; mean interval: 8 months) available biopsy with residual or recurrent BE after ablation. At t = 0, allelic loss was detected of 5q in 27%, 9p in 56%, 17p in 31% and 18q in 6% of informative cases. At t = 1 (18 patients with persistent MET and 3 with LGD) and at t = 2 (8 MET, 2 LGD), the LOH patterns were not statistically different from t = 0. Further, multiple genetic lineages before and after therapy were detected in 15 cases illustrating the multiclonal nature of BE. We conclude that recurrent and/or persistent BE after ablative therapy still contains genetic alterations associated with malignant progression to cancer. Therefore, the goal of treatment should be the complete elimination of Barrett's mucosa. © 2005 Wiley-Liss, Inc. [source]

Stress, norepinephrine and depression

ACTA NEUROPSYCHIATRICA, Issue 4 2002
Brian E. Leonard
Experimental and clinical evidence implicates stress as a major predisposing factor in depression and other severe psychiatric disorders. In this review, evidence is presented to show how the impact of stress on the central sympathetic system leads to changes in the endocrine, immune and neurotransmitter axes which underlie the main clinical symptoms of depression. Thus it can be shown that the noradrenergic system is dysfunctional in depression, a situation which reflects the chronic hypersecretion of glucocorticoids and inflammatory mediators within the brain in addition to an enhanced activity of the locus ceruleus. With regard to the actions of antidepressants in modulating the stress response and alleviating depression it is now evident that, irrespective of the presumed specificity of the antidepressants for the noradrenergic or serotonergic systems, they all normalize noradrenergic function. This action is due partly to the regulation of tyrosine hydroxylase activity in the locus ceruleus but also enhances neuronal sprouting which counteracts the neurodegenerative effects of chronic stress. [source]

Desloratadine partially inhibits the augmented bacterial responses in the sinuses of allergic and infected mice

CLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2004
V. Kirtsreesakul
Summary Background Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis. How AR augments a bacterial infection is unknown. Objective Our purpose in this study was to test whether an H1 receptor antagonist, desloratadine, could reduce the augmented effect of an ongoing allergic reaction on acute bacterial rhinosinusitis. Methods Three groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected and allergic mice treated with desloratadine, (2) infected and allergic mice treated with placebo, and (3) infected mice. A fourth group of uninfected, non-sensitized mice served as a control for the cellular changes. BALB/c mice were sensitized by two intraperitoneal injections of OVA given 8 days apart. One day after the second injection, the mice were nasally exposed daily to 6% OVA (the groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS) (the infection-only group) for 5 days. After the second OVA exposure, the mice were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or placebo was given daily throughout the OVA exposure period. Nasal allergic symptoms were observed by counting of nasal rubbing and sneezing for 10 min after OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was done, and the inflammatory cells in the sinuses were evaluated by flow cytometry. Results Mice that were made allergic, infected, and treated with placebo showed more organisms and phagocytes than did only infect mice. They also manifested allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine treatment during allergen exposure reduced allergic symptoms and reduced sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in the placebo-treated group. Conclusion Desloratadine treatment during nasal challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting that histamine via an H1 receptor plays a role in the augmented infection in mice with an ongoing allergic reaction. [source]

Metastatic pulmonary calcification in a dialysis patient: Case report and a review

HEMODIALYSIS INTERNATIONAL, Issue S2 2006
Christoph H. EGGERT
Abstract A 19-year-old male presented with chest pain and dyspnea. He was anephric following nephrectomy for focal segmental glomerulosclerosis, had a subsequent failed transplant, and had been dialysis dependent for 3 years. Workup revealed hyperparathyroidism and an abnormal chest X-ray and computed tomography scan, significant for massive extra-skeletal pulmonary calcification. A markedly abnormal Technitium99 methylene diphosphonate (Tc99m-MDP) bone scan confirmed the clinical suspicion of metastatic pulmonary calcification. Metastatic pulmonary calcification (MPC) is common, occurring in 60% to 80% of dialysis patients on autopsy and bone scan series. It may lead to impaired oxygenation and restrictive lung disease. Typically, the calcium crystal is whitlockite rather than hydroxyapatite, which occurs in vascular calcification. Four major predisposing factors may contribute to MPC in dialysis patients. First, chronic acidosis leaches calcium from bone. Second, intermittent alkalosis favors deposition of calcium salts. Third, hyperparathyroidism tends to cause bone resorption and intracellular hypercalcemia. Finally, low glomerular filtration rate can cause hyperphosphatemia and an elevated calcium-phosphorus product. There may be other factors. Some authors suggest that the incidence of MPC in recent years may be lower due to improved dialysis techniques. The diagnosis is confirmed by biopsy, but can be suspected by typical findings on a Tc99m-MDP bone scan. Therapy is limited to ensuring adequate dialysis, correcting calcium-phosphorus product, and hyperparathyroidism; discontinuing vitamin D analogues may help. Conflicting reports show that transplantation may either improve or worsen the situation. MPC should be considered in dialysis patients who have characteristic abnormal chest radiography and/or pulmonary symptoms. [source]