Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients

Background

Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection.

Methods

A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control.

Results

TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values.

Conclusions

TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.     

Repeat percutaneous balloon mitral valvotomy vs. mitral valve replacement in patients with restenosis after previous balloon mitral valvotomy and unfavorable valve characteristics

Background:

Symptomatic mitral restenosis develops in up to 21% of patients after percutaneous balloon mitral valvotomy (PBMV), and most of these patients undergo mitral valve replacement (MVR).

Hypothesis:

Repeating PBMV (re‐PBMV) might be an effective and less‐invasive treatment for these patients.

Methods:

Forty‐seven patients with post‐PBMV mitral restenosis and unfavorable valve characteristics were assigned either to re‐PBMV (25 cases; mean age 40.7 ± 11 y, 76% female) or MVR (22 cases; mean age 47 ± 10 y, 69% female) at 51 ± 33 months after the prior PBMV. The mean follow‐up was 41 ± 32 months and 63 ± 30 months for the re‐PBMV and MVR groups, respectively.

Results:

The 2 groups were homogenous in preoperative variables such as gender, echocardiographic findings, and valve characteristics. Patients in the MVR group were older, with a higher mean New York Heart Association functional class, mean mitral valve area, mitral regurgitation grade, and right ventricular systolic pressure (P = 0.03), and more commonly were in AF. There were 3 in‐hospital deaths (all in the MVR group) and 4 during follow‐up (3 in the MVR group and 1 in the re‐PBMV group). Ten‐year survival was significantly higher in re‐PBMV vs MVR (96% vs 72.7%, P<0.05), but event‐free survival was similar (52% vs 50%, P = 1.0) due to high reintervention in the re‐PBMV group (48% vs 18.1%, P = 0.02).

Conclusions:

In a population with predominantly unfavorable characteristics for PBMV, short‐ and long‐term outcomes are both reasonable after re‐PBMV with less mortality but requiring more reinterventions compared with MVR. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes

Aims

This study performed to determine the effects of folate supplementation on indices of glycemic control, insulin resistance and lipid profile in overweight and obese men with type 2 diabetes under metformin (at least 1500 mg daily) treatment.

Methods

The study was a double-blind randomized controlled clinical trial. Forty-eight overweight and obese men (aged 58.2 ± 8.9 years; BMI = 28.6 ± 2.9 kg/m²) with type 2 diabetes participated in the study. Patients were divided randomly into two groups of folic acid (5 mg/d) and placebo. All patients received the tablets for eight weeks.

Results

Supplementation with folic acid led to 8% decrease in HbA1C (p = 0.048), 7.5% in fasting blood glucose (p = 0.051), 16.2% in serum insulin (p = 0.021), 20.5% in insulin resistance (p = 0.041) and 21.2% in plasma homocysteine (p = 0.000). A significant increase in serum folate and B12 levels (19% and 17.3%, p = 0.000, respectively) were observed in the folic acid group, whereas no significant changes occurred in the placebo group. Also, in the folic acid and placebo groups, there were no significant changes in body weight.

Conclusions

Folic acid supplementation lowered plasma level of homocysteine, improved glycemic control and insulin resistance in patients with type 2 diabetes.     

New and unusual O alleles at the ABO locus are implicated in unexpected blood group phenotypes

BACKGROUND: In the ABO blood group system mutations in the A gene may lead to weak A subgroups owing to a dysfunctional 3-alpha-N-acetylgalactosaminyltransferase. STUDY DESIGN AND METHODS: Blood and DNA were investigated to correlate weak A phenotypes with genotype, and an overrepresentation of the infrequent O2 allele was observed. Consequently, 57 available O2 alleles were examined in detail. RESULTS: Two new O2 alleles were identified having mutations resulting in Gly229Asp with or without Arg217Cys. A recently described O2 variant (488C>T; Thr163Met) was also found. Surprisingly, both the original and the variant O2 alleles were associated with either O or Aweak phenotypes. Three novel O alleles surfaced in six other samples with suspected A subgroups. These were A1-like alleles having nonsense mutations causing premature truncation at codons 56, 107, or 181. A second example of the rare O3 allele was also identified. A newly described O1 allele having 768C>A was found to be the third most frequent O allele among Swedish donors. Of the five novel O alleles, three were incorrectly interpreted as A1 following routine ABO genotyping. CONCLUSION: Apparent O alleles lacking 261delG may cause weak A expression on red blood cells and/or inhibit anti-A production. A hypothesis that exchange of genetic material between principally dissimilar O alleles during mitosis ("autologous chimerism") restores glycosyltransferase activity in some cells would explain this interesting phenomenon.     

Breastfeeding and Helicobacter pylori Infection in Early Childhood: a Continuing Dilemma

Objective:

Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in humans. Chronic colonization increases the risk of duodenal ulcer and gastric cancer. The risk factors for acquiring the infection have been extensively studied. However, there are conflicting results on the role of breastfeeding in the prevention of H. pylori infection. We conducted a study to evaluate the effects of breastfeeding on the H. Pylori infection in Kurdish children in Sanandaj, IR Iran.

Methods:

A historical cohort study was carried out from January 2011 through December 2012. Totally 221 children who were going to attain 2 years old during the study period were randomly enrolled. They were divided into two groups, i.e. breastfed and non-breastfed. We used H. pylori stool antigen test to detect infection in the selected group of children after age of 2 years and cessation of breastfeeding. Each group was subdivided into two subgroups, infected and non-infected. The associations of breastfeeding with H. pylori infection was assessed using statistical software.

Findings:

We found no difference in the odds of infection between breastfed and non-breastfed groups (OR=0.809, 95% CI [0.453–1.444]). An association between age and the prevalence of infection was found (P=0.008). There was an increase in the odds of infection as the family size grew (OR=1.93, 95% CI [1.04–3.6]) as well as increasing housing density (OR=2.12, 95% CI [1.10–4.10]).

Conclusion:

The data suggests that breastfeeding in infancy does not protect against H. pylori infection for long duration among studied children in Iran. The protective effects of breastfeeding, if any, are at most transient.     

A large population-based study on the prevalence of electrocardiographic abnormalities: A result of Mashhad stroke and heart atherosclerotic disorder cohort study

Background

Twelve-lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population.

Methods

ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS.

Results

Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T-wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff-Parkinson-White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T-wave abnormalities, Wolff-Parkinson-White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P-wave duration, and QRS duration between men and women indicated that there was a significant difference.

Conclusions

Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups.     

Association of the R92Q TNFRSF1A mutation and extracranial deep vein thrombosis in patients with Behçet's disease

OBJECTIVE: Beh?et's disease is a chronic, relapsing, multisystemic inflammatory disorder characterized by recurrent oral and genital ulcers and by ocular, articular, vascular, and central nervous system involvement. The tumor necrosis factor alpha (TNFalpha) pathway is likely involved in the pathophysiology of Beh?et's disease. One of the 2 TNFalpha receptors is TNF receptor superfamily 1A (TNFRSF1A). We searched for R92Q TNFRSF1A mutations in patients with Beh?et's disease. METHODS: A search for TNFRSF1A mutations was performed by polymerase chain reaction amplification of the TNFRSF1A gene, followed by denaturing high-performance liquid chromatography scanning. RESULTS: Among the 74 unrelated European patients with Beh?et's disease, 5 (6.8%) carried the R92Q TNFRSF1A mutation. The frequency of the R92Q mutation in patients with Beh?et's disease was significantly higher than that in controls (P = 0.006 by Fisher's exact test). Deep vein thrombosis was significantly associated with the R92Q mutation (P = 0.001 [with Bonferroni adjustment for multiple comparisons]). Among the 30 patients with thrombosis, 10 had cerebral thrombophlebitis. None of these patients had the R92Q mutation. Among the 20 patients with Beh?et's disease who had extracranial deep vein thrombosis, 6 had the R92Q mutation, whereas 14 did not (P < 0.0001) CONCLUSION: The R92Q mutation in patients with Beh?et's disease is associated with an increased risk of extracranial venous thrombosis. This new finding may help in understanding the complex prothrombotic state in patients with Beh?et's disease.