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Rabijewski M.,Medical University of Warsaw | Papierska L.,Medical Center for Postgraduate Education | Piatkiewicz P.,Medical University of Warsaw
Aging Male | Year: 2015

Objectives: Around 40% of diabetic men have lowered testosterone and symptoms of hypogonadism but the prevalence of hypogonadism among prediabetic men is unknown. The aim of this study was to investigate the prevalence of late-onset hypogonadism (LOH) in population of Polish men with prediabetes. Methods: This study was performed in 196 prediabetic men and in 184 normoglycemic, control group. Prediabetes was defined as impaired fasting glucose, impaired glucose tolerance and/or HbA1c 5.7-6.4%. LOH was defined as low libido, diminished frequency of morning erections and erectile dysfunctions in men with total testosterone <12nmol/l. Results: Total testosterone (TT) level in prediabetes group was 11.78±1.76 and 16.37±1.6nmol/l in control group (p<0.001). LOH was diagnosed in 30% prediabetic men and in 13.6% control men. There were negative relationships between calculated free testosterone (cFT) and HbA1c (r=-0.3856; p<0.005). In prediabetic group, TT and cFT levels were lower in patients with impaired glucose tolerance than impaired fasting glucose (p<0.05 and p<0.02, respectively). We showed inverse relationships between IIEF-5 score and cFT (r=-0.414, p<0.005) and between IIEF-5 and HbA1c (r=-0.395, p<0.002). Conclusions: In population of Polish men with prediabetes we observed high prevalence of LOH. Routine testosterone screening should be performed in all prediabetic men. © 2015 Informa UK Ltd. All rights reserved.

Czajka-Oraniec I.,Medical Center for Postgraduate Education | Simpson E.R.,Prince Henrys Institute
Endokrynologia Polska | Year: 2010

Aromatase is a member of the cytochrome P450 superfamily that catalyzes the conversion of androgens (C19), namely testosterone and androstenedione, into oestrogens (C18), oestradiol, and oestrone, respectively. The enzyme is active in various tissues in both females and males, thus oestrogens are produced not only in gonads but also in extra-gonadal localizations such as brain, adipose tissue, breast, skin, and bone. Aromatase gene CYP19A1 located on chromosome 15 comprises nine coding exons and a number of alternative non-coding first exons that regulate tissue-specific expression. Studies on local regulation of aromatase expression and activity are important for understanding processes such as growth of oestrogen-dependent breast cancer. Rare clinical conditions of aromatase deficiency and excess have revealed some new and unexpected oestrogen functions in metabolism and bone health in both women and men. They were further studied using transgenic animal models such as aromatase knockout mice (ArKO) or (AROM+) mice overexpressing human aromatase. Research on aromatase was important for its practical outcome as it contributed to the development of aromatase inhibitors (Als), an effective and safe group of drugs for the first-line endocrine therapy of breast cancer. Further studies are needed to establish Als application in other oestrogen-dependent conditions, to overcome the resistance in breast cancer patients, and to develop tissue-specific selective inhibitors.

Robertson D.J.,Medical Center | Kaminski M.F.,Medical Center for Postgraduate Education | Kaminski M.F.,Center of Oncology of Poland | Kaminski M.F.,University of Oslo | Bretthauer M.,University of Oslo
Gut | Year: 2015

Screening for colorectal cancer has been proven to be effective in reducing colorectal cancer incidence and mortality. While the precise benefit of screening exclusively by colonoscopy is not yet known, unarguably, the exam is central to the success of any screening programme. The test affords the opportunity to detect and resect neoplasia across the entire large bowel and is the definitive examination when other screening tests are positive. However, colonoscopy is invasive and often requires sedation as well as extensive bowel preparation, all of which puts the patient at risk. Furthermore, the test can technically be demanding and, unarguably, there is variation in how it is performed. This variation in performance has now been definitively linked to important outcome measures. For example, interval cancers are more common in low adenoma detectors as compared with high adenoma detectors. This review outlines the most current thinking regarding the effectiveness of colonoscopy as a screening tool. It also outlines key concepts to optimise its performance through robust quality assurance programmes and high-quality training.

Johnson E.M.,Vanderbilt University | Gaddy J.A.,Vanderbilt University | Voss B.J.,Vanderbilt University | Hennig E.E.,Medical Center for Postgraduate Education | And 2 more authors.
Infection and Immunity | Year: 2014

Helicobacter pylori causes numerous alterations in gastric epithelial cells through processes that are dependent on activity of the cag type IV secretion system (T4SS). Filamentous structures termed "pili" have been visualized at the interface between H. pylori and gastric epithelial cells, and previous studies suggested that pilus formation is dependent on the presence of the cag pathogenicity island (PAI). Thus far, there has been relatively little effort to identify specific genes that are required for pilus formation, and the role of pili in T4SS function is unclear. In this study, we selected 7 genes in the cag PAI that are known to be required for T4SS function and investigated whether these genes were required for pilus formation. cagT, cagX, cagV, cagM, and cag3 mutants were defective in both T4SS function and pilus formation; complemented mutants regained T4SS function and the capacity for pilus formation. cagY and cagC mutants were defective in T4SS function but retained the capacity for pilus formation. These results define a set of cag PAI genes that are required for both pilus biogenesis and T4SS function and reveal that these processes can be uncoupled in specific mutant strains. © 2014, American Society for Microbiology.

Hu M.I.,University of Houston | Glezerman I.,Sloan Kettering Cancer Center | Leboulleux S.,Institute Gustave Roussy | Insogna K.,Yale University | And 5 more authors.
Journal of the National Cancer Institute | Year: 2013

Hypercalcemia of malignancy (HCM), caused primarily by tumor-induced bone resorption, may lead to renal failure, coma, and death. Although HCM can be treated with intravenous bisphosphonates, patients may not respond or may relapse on therapy. Denosumab binds the bone resorption mediator RANKL. In this single-arm, open-label, proof-of-concept study, HCM patients with albumin-corrected serum calcium (CSC) levels greater than 12.5 mg/dL (Common Terminology Criteria for Adverse Events grade ≥3) despite recent intravenous bisphosphonate treatment received subcutaneous denosumab on days 1, 8, 15, and 29, and then every 4 weeks. The primary endpoint was the proportion of patients with CSC 11.5 mg/dL or less (grade ≤1) within 10 days of denosumab initiation. In a prespecified interim analysis, 15 patients received denosumab (median CSC = 13.6 mg/dL). Time to response and response duration were analyzed with Kaplan-Meier methods. All statistical tests were two-sided. By day 10, 12 patients (80%; 95% exact confidence interval [CI] = 52% to 96%) responded (CSC ≤11.5 mg/dL); median response duration was 26 days. Ten patients (67%; 95% exact CI = 38% to 88%) had complete responses (CSC ≤10.8 mg/dL) by day 10. Denosumab may offer a new treatment option for HCM. © The Author 2013.

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