Preoperative staging of colorectal cancer using virtual colonoscopy: correlation with surgical results

The aim of this study was to evaluate the clinical usefulness of computed tomography colonography (CTC) in the preoperative staging in patients with abdominal pain for occlusive colorectal cancer (CRC) and to compare the results of CTC with the surgical ones

A Functional 12T-insertion polymorphism in the <i>ATP1A1</i> promoter confers decreased susceptibility to hypertension in a male Sardinian population

Identification of susceptibility genes for essential hypertension in humans has been a challenge due to its multifactorial pathogenesis complicated by gene-gene and gene-environment interactions, developmental programing and sex specific differences. These concurrent features make identification of causal hypertension susceptibility genes with a single approach difficult, thus requiring multiple lines of evidence involving genetic, biochemical and biological experimentation to establish causal functional mutations. Here we report experimental evidence encompassing genetic, biochemical and in vivo modeling that altogether support ATP1A1 as a hypertension susceptibility gene in males in Sardinia, Italy. ATP1A1 encodes the α1Na,K-ATPase isoform, the sole sodium pump in vascular endothelial and renal tubular epithelial cells. DNA-sequencing detected a 12-nucleotide long thymidine (12T) insertion(ins)/deletion(del) polymorphism within a poly-T sequence (38T vs 26T) in the ATP1A1 5’-regulatory region associated with hypertension in a male Sardinian population. The 12T-insertion allele confers decreased susceptibility to hypertension (P = 0.035; OR = 0.50 [0.28–0.93]) accounting for 12.1 mmHg decrease in systolic BP (P = 0.02) and 6.6 mmHg in diastolic BP (P = 0.046). The ATP1A1 promoter containing the 12T-insertion exhibited decreased transcriptional activity in in vitro reporter-assay systems, indicating decreased α1Na,K-ATPase expression with the 12T-insertion, compared with the 12T-deletion ATP1A1 promoter. To test the effects of decreased α1Na,K-ATPase expression on blood pressure, we measured blood pressure by radiotelemetry in three month-old, highly inbred heterozygous knockout ATP1A1+/− male mice with resultant 58% reduction in ATP1A1 protein levels. Male ATP1A1+/− mice showed significantly lower blood pressure (P &#60; 0.03) than age-matched male wild-type littermate controls. Concordantly, lower ATP1A1 expression is expected to lower Na-reabsorption in the kidney thereby decreasing sodium-associated risk for hypertension and sodium-induced endothelial stiffness and dysfunction. Altogether, data support ATP1A1 as a hypertension susceptibility gene in a male Sardinian population, and mandate further investigation of its involvement in hypertension in the general population

Genome-Wide Meta-Analysis of Blood Pressure Response to beta(1)- Blockers : Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies

Background-There exists a wide interindividual variability in blood pressure (BP) response to beta(1)-blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome-wide meta-analysis of genetic variants beta(1)-influencing blocker BP response. Methods and Results-Genome-wide association analysis for systolic BP and diastolic BP response to beta(1)-blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta-analysis and single nucleotide polymorphisms (SNPs) with P Conclusions-Data from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with beta(1)-blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.Peer reviewe

A functional 12T-insertion polymorphism in the ATP1A1 promoter confers decreased susceptibility to hypertension in a male Sardinian population.

Identification of susceptibility genes for essential hypertension in humans has been a challenge due to its multifactorial pathogenesis complicated by gene-gene and gene-environment interactions, developmental programing and sex specific differences. These concurrent features make identification of causal hypertension susceptibility genes with a single approach difficult, thus requiring multiple lines of evidence involving genetic, biochemical and biological experimentation to establish causal functional mutations. Here we report experimental evidence encompassing genetic, biochemical and in vivo modeling that altogether support ATP1A1 as a hypertension susceptibility gene in males in Sardinia, Italy. ATP1A1 encodes the α1Na,K-ATPase isoform, the sole sodium pump in vascular endothelial and renal tubular epithelial cells. DNA-sequencing detected a 12-nucleotide long thymidine (12T) insertion(ins)/deletion(del) polymorphism within a poly-T sequence (38T vs 26T) in the ATP1A1 5'-regulatory region associated with hypertension in a male Sardinian population. The 12T-insertion allele confers decreased susceptibility to hypertension (P = 0.035; OR = 0.50 [0.28-0.93]) accounting for 12.1 mmHg decrease in systolic BP (P = 0.02) and 6.6 mmHg in diastolic BP (P = 0.046). The ATP1A1 promoter containing the 12T-insertion exhibited decreased transcriptional activity in in vitro reporter-assay systems, indicating decreased α1Na,K-ATPase expression with the 12T-insertion, compared with the 12T-deletion ATP1A1 promoter. To test the effects of decreased α1Na,K-ATPase expression on blood pressure, we measured blood pressure by radiotelemetry in three month-old, highly inbred heterozygous knockout ATP1A1+/- male mice with resultant 58% reduction in ATP1A1 protein levels. Male ATP1A1+/- mice showed significantly lower blood pressure (P < 0.03) than age-matched male wild-type littermate controls. Concordantly, lower ATP1A1 expression is expected to lower Na-reabsorption in the kidney thereby decreasing sodium-associated risk for hypertension and sodium-induced endothelial stiffness and dysfunction. Altogether, data support ATP1A1 as a hypertension susceptibility gene in a male Sardinian population, and mandate further investigation of its involvement in hypertension in the general population

Primary colonic lymphoma: An incidental finding in a patient with a gallstone attack

We report a case of primary colonic lymphoma incidentally diagnosed in a patient presenting a gallbladder attack making particular attention on the diagnostic findings at ultrasound (US) and total body computed tomography (CT) exams that allowed us to make the correct final diagnosis. A 85-year-old Caucasian male patient was referred to our department due to acute pain at the upper right quadrant, spreaded to the right shoulder blade. Patient had nausea and mild fever and Murphy's maneuver was positive. At physical examination a large bulky mass was found in the right flank. Patient underwent to US exam that detected a big stone in the lumen of the gallbladder and in correspondence of the palpable mass, an extended concentric thickening of the colic wall. CT scan was performed and confirmed a widespread and concentric thickening of the wall of the ascending colon and cecum. In addition, revealed signs of microperforation of the colic wall. Numerous large lymphadenopathies were found in the abdominal, pelvic and thoracic cavity and there was a condition of splenomegaly, with some ischemic outcomes in the context of the spleen. No metastasis in the parenchimatous organs were found. These imaging findings suggest us the diagnosis of lymphoma. Patient underwent to surgery, and right hemicolectomy and cholecystectomy was performed. Histological examination confirmed our diagnosis, revealing a diffuse large B-cell lymphoma. The patient underwent to Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone chemotherapy showing only a partial regression of the lymphadenopathies, being in advanced stage at the time of diagnosis

Bilateral Adrenal Hemorrhage in a Patient with Myelodysplastic Syndrome: Value of MRI in the Differential Diagnosis

Bilateral adrenal hemorrhage is a rare potentially life-threatening event that occurs either in traumatic or nontraumatic conditions. The diagnosis is often complicated by its nonspecific presentation and its tendency to intervene in stressful critical illnesses. Due to many disorders in platelet function, hemorrhage is a major cause of morbidity and mortality in patients affected by myeloproliferative diseases. We report here the computed tomography and magnetic resonance imaging findings of a rare case of bilateral adrenal hemorrhage in a patient with myelodysplastic syndrome, emphasizing the importance of MRI in the differential diagnosis

Characteristics of the study population.

<p>Characteristics of the study population.</p

Analysis of <i>ATP1A1</i> (12T-ins/del) variants based on blood pressure as a quantitative trait.

<p>Blood pressures were adjusted for age, body mass index and case/control status.</p><p>^a Number of individuals</p><p>^b Systolic blood pressure in mmHg</p><p>^c Diastolic blood pressure in mmHg</p><p>s.e.m., standard error of the mean</p><p>Δ SBP, difference in systolic blood pressure</p><p>Δ DBP, difference in diastolic blood pressure</p><p><i>P</i>, Mann-Whitney Rank Sum Test <i>P</i> values.</p><p>Analysis of <i>ATP1A1</i> (12T-ins/del) variants based on blood pressure as a quantitative trait.</p

Analysis of ATP1A1 protein expression, blood pressure, heart rate and activity in heterozygous <i>ATP1A1^+/−</i> and wild-type male mice.

<p>(A) Western blot analysis of <i>ATP1A1^+/−</i> and wild type mouse whole kidney extracts (30 μg) reacted with anti-mouse ATP1A1 and anti-mouse βActin polypeptides. (B) Densitometry analysis of samples shown in (A) detecting 58% decrease ATP1A1 levels in <i>ATP1A1^+/−</i> kidneys. (C) Mean systolic blood pressure ± sem (SBP; mmHg). (D) Mean heart rate ± sem (beats/min; BPM). (E) Mean activity ± sem (Counts/min) in <i>ATP1A1^+/−</i> (solid bars, n = 4) and wild-type (open bars, n = 5) male mice. * <i>P</i> < 0.03, ** <i>P</i> = 0.015 (two-tailed student <i>t</i>-test).</p

Identification of the 12T-ins/del polymorphism in the <i>ATP1A1</i> promoter region and transcriptional activity of <i>ATP1A1</i> promoter variants.

<p>(A) Nucleotide sequence spanning the poly-T sequence involved in the 12T-ins/del polymorphism from the two <i>ATP1A1</i> (p12T ins, p12T del) reporter gene constructs utilized in the transcriptional assays. On right detection of 12T-insertion and 12T-deletion alleles by PCR-amplification followed by denaturing polyacrylamide gel (6%) electrophoresis used for genotyping of the Sardinian cohort. (B) Illustration of the <i>ATP1A1</i> promoter region. Non-coding exon is presented as open box and exon encoding the NH₂-terminal region is presented as black box. Sequence and location of the <i>ATP1A1</i> 12T-ins/del polymorphism is shown. The positions of TATAAA box, INR (initiator) and DPE (downstream promoter element) core promoter elements within <i>ATP1A1</i> promoter are shown. Core promoter elements were identified based on 100% homology with corresponding consensus sequences [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116724#pone.0116724.ref039" target="_blank">39</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0116724#pone.0116724.ref040" target="_blank">40</a>]. (C) Schematic of two <i>ATP1A1</i> (p12T ins, p12T del) reporter gene constructs. (D) Relative transcriptional activity of 12T-insertion (p12T ins) and 12T-deletion (p12T del) gene constructs in Cos1, HEK293 and MDA-MB-468 cells. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01 (two-tailed student <i>t</i>-test).</p