Improvement of Cardiac Function After Roux-en-Y Gastric Bypass in Morbidly Obese Patients Without Cardiac History Measured by Cardiac MRI.

Purpose: Metabolic syndrome in patients with morbid obesity causes a higher cardiovascular morbidity, eventually leading to left ventricular hypertrophy and decreased left ventricular ejection fraction (LVEF). Roux-en-Y gastric bypass (RYGB) is considered the gold standard modality for treatment of morbid obesity and might even lead to improved cardiac function. Our objective is to investigate whether cardiac function in patients with morbid obesity improves after RYGB.

Correction to: Age-Related Effects of Bariatric Surgery on Early Atherosclerosis and Cardiovascular Risk Reduction.

Frederik H. W. Jonker and Vera A.

Age-Related Effects of Bariatric Surgery on Early Atherosclerosis and Cardiovascular Risk Reduction.

Background: Carotid intima-media thickness (CIMT) is increasingly used as a prognostic indicator for early atherosclerosis and the development of cardiovascular disease. The objective of this study is to assess the exact effects of bariatric surgery on CIMT reduction in different age groups.

Methods: CIMT was measured just proximal to the bifurcation of the carotid artery in 166 patients with mean body mass index of 43.

The basilic vein and the cephalic vein perform equally in upper arm arteriovenous fistulae.

Objective: To compare the brachiocephalic (BC) and basilic vein transposition (BVT) arteriovenous fistula (AVF) with regard to maturation, patency, blood flow and complication rates.

Design: A retrospective chart review.

Materials And Method: Between January 2000 and December 2010, consecutive patients undergoing BC or BVT AVF were included.

Fetal and postnatal growth and blood pressure at the age of 2 years. The Generation R Study.

Objectives: To examine which fetal and postnatal growth characteristics are associated with blood pressure (BP) in children at the age of 2 years.

Methods: This study was embedded in the Generation R Study, a population-based prospective cohort study from early fetal life onwards. Fetal ultrasound examinations were carried out at the visits in one of the research centers in early, mid- and late pregnancy.

Fetal and postnatal growth and body composition at 6 months of age.

Objectives: The objectives of the study was to examine which parental, fetal, and postnatal characteristics are associated with fat and lean mass at the age of 6 months and examine the effect of growth (catch-down, catch-up) in fetal life and early infancy on fat and lean mass.

Design: This study was embedded in the Generation R Study, a prospective cohort study from early fetal life onward. Body composition was measured by dual-energy X-ray absorptiometry in 252 infants at 6 months.

A variant of the IGF-I gene is associated with blood pressure but not with left heart dimensions at the age of 2 years: the Generation R Study.

Background And Objective: A common variant of the IGF-I gene has been shown to be associated with cardiovascular disease in adulthood. The objective of this study was to examine whether this variant of the IGF-I gene is associated with blood pressure and left heart dimensions in early childhood.

Research Design And Methods: This study was embedded in the Generation R Study, a population-based prospective cohort study from foetal life onwards.

Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels.

Colorectal cancer (CRC) resistance to fluoropyrimidines and other inhibitors of thymidylate synthase (TS) is a serious clinical problem often associated with increased intracellular levels of TS. Since the tumour suppressor gene p53, which is mutated in 50% of CRC, regulates the expression of several genes, it may modulate TS activity, and changes in the status of p53 might be responsible for chemoresistance. Therefore, this study was aimed to investigate TS levels and sensitivity to TS inhibitors in wild-type (wt) and mutant (mt) p53 CRC cells, Lovo and WiDr, respectively, transfected with mt and wt p53.

Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study.

Purpose: Approximately 10-30% of surgically treated head and neck cancer patients develop local recurrences while the resection margins are histologically tumor free. These recurrences may arise from cancer cells left behind but not detected by the pathologist, or they may develop from precursor lesions adjacent to the tumor that were not completely resected. We have investigated whether TP53-mutated DNA in the surgical margins is suitable to identify patients with head and neck squamous cell carcinoma at risk for local and locoregional recurrence.

Thymidylate synthase inhibition triggers apoptosis via caspases-8 and -9 in both wild-type and mutant p53 colon cancer cell lines.

Thymidylate synthase (TS) is an important target for chemotherapy and increased levels are associated with resistance to colorectal cancer chemotherapy. TS can be inhibited by 5-fluorouracil (5-FU) and antifolates, ultimately resulting in apoptosis. We aimed to clarify whether activation of caspases and Fas signalling are crucial for the onset of apoptosis after specific inhibition of TS and whether p53 plays a role in activation of these downstream processes.

Mutated p53 as a molecular marker for the diagnosis of head and neck cancer.

In total, 10-30% of patients with head and neck squamous cell carcinoma (HNSCC) develop local recurrences despite seemingly adequate tumour resection. This may result from minimal residual cancer (MRC): small numbers of tumour cells left behind in the surgical margins, undetectable by routine histopathology. In recent studies, p53 mutations have been considered as selective and sensitive DNA markers of cancer cells.

Specific p53 immunostaining patterns are associated with smoking habits in patients with oral squamous cell carcinomas.

Aims: To identify immunostaining patterns that are predictive for p53 mutations and to investigate whether p53 mutations are associated with established risk factors for oral squamous cell carcinoma (OSCC).

Methods: Fifty five OSCCs were investigated for p53 protein expression by immunohistochemistry (IHC). Ten of these cases, including five p53 immunopositive and five p53 immunonegative cases, were subjected to microdissection of representative tumour areas followed by sequence analysis for the detection of TP53 mutations.

Time-dependent changes in factors involved in the apoptotic process in human ovarian cancer cells as a response to cisplatin.

Objectives: Apoptosis is believed to be a major mechanism of cisplatin-induced cell death. We investigated the kinetics of apoptosis in four human ovarian cancer cell lines treated with cisplatin to obtain insight into the role and the behavior of a variety of factors involved in this process.

Methods: The cell lines A2780, H134, and IGROV-1 (all wild-type p53) and OVCAR-3 (mutant p53) were exposed to cisplatin for 1 h and the antiproliferative effects were measured after 96 h.

Discordance of genetic alterations between primary head and neck tumors and corresponding metastases associated with mutational status of the TP53 gene.

Ample molecular data are available on the progression from normal mucosa to invasive head and neck squamous cell carcinoma (HNSCC), but information on further genetic progression to metastatic disease is scarce. To obtain insight into the metastatic process, we compared 23 primary HNSCCs with 25 corresponding lymph node metastases (LNMs) and 10 corresponding distant metastases (DMs) with respect to TP53 mutations and patterns of loss of heterozygosity (LOH) based on 26 microsatellite markers on six chromosome arms (3p, 9p, 17p, 13q, 8p, and 18q). In 18 of the 23 patients, a TP53 mutation was detected in the primary tumor, and in all cases the same TP53 mutation was present in the corresponding LNM or DM.

Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas.

High-risk human papillomaviruses (HPVs) have been proposed to be associated with a subset of head and neck cancers (HNSCCs). However, clear biological evidence linking HPV-mediated oncogenesis to the development of HNSCC is hardly available. An important biological mechanism underlying HPV-mediated carcinogenesis is the inactivation of p53 by the HPV E6 oncoprotein.

Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications.

In 1953, Slaughter et al. [D. P.

Molecular assays for the diagnosis of minimal residual head-and-neck cancer: methods, reliability, pitfalls, and solutions.

The prognosis of cancer patients is determined by the radicalness of treatment: residual tumor cells will grow out and develop in manifest local recurrences, regional recurrences, and distant metastases. Classical diagnostic methods such as radiology and histopathology have limited sensitivities, and only by molecular techniques can minimal residual disease be detected. In tissue samples containing the normal tissue counterpart of a tumor, only tumor-specific markers can be exploited, whereas in other samples, tissue-specific markers can be used.

Molecular diagnosis of head and neck cancer.

Patients with advanced stages of head and neck cancer frequently develop locoregional recurrence as well as distant metastases. These data indicate that traditional diagnostic methods such as histopathology and radiology are not sensitive enough to detect the small numbers of tumor cells which are left behind, defined as minimal residual disease (MRD). Sensitive diagnostic assays based on molecular markers appear to be powerful tools to improve the staging of these patients.