Search

Lynch syndrome is an inherited cancer syndrome caused by germline mutations in mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. LS predisposes to high risk of early-onset colorectal, endometrial and other tumors. Patients with Lynch syndrome have also been shown to have an elevated risk for pancreatic cancer (PC). In this study, we aimed to estimate the frequency of suspected Lynch syndrome among a series of 135 PC patients. Further, we wanted to determine the frequency of MMR gene mutations in the suspected Lynch syndrome cases. We also aimed to verify the pathogenicity of any novel non-truncating variants we might detect with a functional assay. Based on personal and/or familial cancer history, 19 patients were classified as suspected Lynch syndrome cases. DNA material for mutation analysis was available for eleven of them. Four patients were found to carry a total of five MLH1 or MSH2 variants. Of these, MSH2-Q402X, MSH2-G322D, and MLH1-K618A had been previously reported, while the MSH2-E205Q and MSH2-V367I variants were novel. MSH2-Q402X is a known stop mutation and reported here for the first time here in association with PC. MLH1-K618A was found in the unaffected branch of a kindred, suggesting that it may be a polymorphism or a low penetrance variant. MSH2-G322D likely does not cause a MMR defect, although this variant has also been associated with breast cancer as indeed seen in our patient. The novel variants MSH2-E205Q and MSH2-V367I were found in the same patient. Both novel variants were however functional in the applied MMR assay. Our findings suggest that only a small subset of pancreatic cancer patients carry pathogenic MMR mutations. [ABSTRACT FROM AUTHOR]

The present investigation was aimed at determining the prevalence and the blood pressure (BP) profile of isolated ambulatory hypertension, defined as an elevated ambulatory BP with normal office blood pressure, in a series of 1488 consecutive outpatients referred for routine clinical evaluation of suspected or established arterial hypertension. All patients underwent both office BP (OBP) measurement by a physician and 24-h ambulatory blood pressure monitoring (ABPM). Using OBP values (cutoff for diagnosis of hypertension?140/90?mmHg) and daytime ABPM (cutoff for diagnosis of hypertension?135/85?mmHg), patients were classified into eight subgroups. In the whole series we found that, independent of treatment status, the prevalence of isolated ambulatory hypertension exceeded 10%. More importantly, 45.3%of individuals who presented with normal OBP values, showed elevated BP at ABPM. Night-time BP, 24-h pulse pressure, and BP variability were significantly higher in isolated ambulatory hypertensives than in normotensive or in white-coat hypertensive individuals. Therefore, isolated ambulatory hypertension is characterized by a blood pressure profile that is similar to that observed in sustained hypertension. These findings suggest that isolated ambulatory hypertension is very common and probably the indications for ABPM should be more extensive in outpatients referred to hypertensive centre.Journal of Human Hypertension (2004) 18, 897-903. doi:10.1038/sj.jhh.1001756 Published online 8 July 2004 [ABSTRACT FROM AUTHOR]

The positive inotropic effect of dopamine has been studied in isolated ventricular strips of guinea-pig heart. The concentration-inotropic response curve for dopamine was significantly shifted to the right by pretreatment with reserpine. In preparations obtained from animals pretreated with reserpine (2.5 mg/kg, 24 h prior to the experiment) the dose-response curve was not significantly affected by haloperidol, a dopamine vascular receptor antagonist (10−3×10 M). The inotropic effect of dopamine was antagonized by practolol (3×10−10 M), but not by phentolamine (3×10−10 M); moreover the alpha-adrenoceptor blocking drug (10 M) did not affect the curve for dopamine in the presence of practolol (3×10 M). In preparations in which fast sodium channels were blocked by K-rich medium, slow electrical responses (calcium-mediated action potentials) as well as contractions were induced by high concentrations of dopamine (10−3×10 M); again these responses were unaffected by phentolamine or haloperidol, but were blocked by practolol. It was concluded that in the guinea-pig ventricular muscle dopamine induced a positive inotropic effect through both indirect and direct action, and that the latter is due to the activation of beta-adrenoceptors. [ABSTRACT FROM AUTHOR]

Copyright of Il Nuovo Cimento della Societa Italiana di Fisica: D is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Il Nuovo Cimento della Societa Italiana di Fisica: D is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Il Nuovo Cimento: B is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Il Nuovo Cimento della Societa Italiana di Fisica: B is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)