Archives of Medical Research - Articles in Press

Expression of Syndecan-1 in Papillary Carcinoma of the Thyroid with Extracapsular Invasion - Corrected Proof

2010-03-15

Background: Syndecan-1 (SDC-1) is a member of the family of transmembrane heparan sulfate proteoglycans, which are involved in cell-cell adhesion and the interaction of cells with the extracellular matrix. Evidence suggests that loss of SDC-1 expression in several benign and malignant epithelial neoplasms is an unfavorable prognostic indicator, but its expression profile in thyroid gland neoplasms remains to be elucidated. The aim of this study was to evaluate SDC-1 expression in papillary carcinomas of the thyroid (PCT) that were both larger and smaller (papillary microcarcinoma) than 10mm, with or without extracapsular extension (PCT-E and PCT-NE).Methods: The expression of SDC-1 was studied in 62 cases of PCT-E and PCT-NE using a tissue microarrays technique (TMA). SDC-1 positivity was predominantly observed in the cytoplasm of neoplastic epithelial cells and in the stroma of PCT.Results: SDC-1 is expressed in both neoplastic epithelial cells and the stroma. It is more frequently expressed in PCT-E than PCT-NE (p=0.002) and the stromal expression of SDC-1 is more intense in PCT-E that are >10mm (p=0.026).Conclusions: The epithelial and stromal expression of SDC-1 observed in this series of PCT suggests that the expression of this protein may be related to extracapsular invasion.

Effect of Eradication of Helicobacter pylori and Iron Supplementation on the Iron Status of Children with Iron Deficiency - Corrected Proof

2010-03-15

Background and Aims: We undertook this study to evaluate the effect of Helicobacter pylori eradication and iron supplementation on the iron nutritional status in children with iron deficiency.Methods: Seven hundred and one children from four public schools in Mexico City were screened to evaluate their iron status. Of them, 72 children with iron deficiency or with anemia were included in this study and were tested for H. pylori infection. Those infected were given eradication treatment and were randomly assigned to daily supplementation for 3 months with ferrous sulfate or placebo. Noninfected children received ferrous sulfate. At the end of the interventions, blood samples were drawn to evaluate their effects on the nutritional status of iron.Results: Thirty eight children with iron deficiency or anemia were infected by H. pylori at baseline. The eradication rate was 86.8%. Children in whom H. pylori eradication was achieved showed an increase of 0.37g/dL (95% CI −0.02, 0.75) on the hemoglobin mean concentration compared to the noninfected children. Children who achieved H. pylori eradication and received ferrous sulfate supplementation showed an increase of 0.47g/dL (95% CI 0.01–0.93) on the hemoglobin mean concentration compared to the noninfected children who received iron supplementation. Noninfected children supplemented with ferrous sulfate showed an increase in ferritin concentration of 11.26 ng/mL (95% CI 1.86–20.65) compared to those who were given the placebo.Conclusions: Our results suggest that the eradication of H. pylori plus iron supplementation increases the pool of functional iron. And that iron supplementation increases the storage of iron in school-age children with iron deficiency.

Multiple Correlations Between Cord Blood Leptin Concentration and Indices of Neonatal Growth - Corrected Proof

2010-03-15

Background: The discovery of a role for leptin in controlling fetal and neonatal growth suggests a fetal origin of some adult chronic diseases and has stimulated research into the mechanisms of action of leptin early in life. The aim of this study was to determine umbilical cord blood leptin levels and to evaluate their association with newborn growth indices.Methods: Two hundred healthy newborns (89 males, 110 females, and one of undetermined gender; gestational ages ranging from 34–43 weeks) and their healthy mothers were enrolled in this study conducted at Moovsavi Hospital in Zanjan, Iran. The body size index of each newborn was determined in terms of birth weight, birth length, head circumference, body mass index (BMI) and ponderal index. Umbilical cord blood leptin levels were measured by ELISA.Results: Umbilical cord leptin concentration was found to positively correlate with birth weight (r=0.322; p<0.0001), neonatal BMI (r=0.247; p<0.0001), ponderal index (r=0.206; p=0.04), and gestational age (r=0.221; p=0.002). There was no significant correlation between cord leptin and birth length or umbilical glucose concentration. Umbilical cord leptin concentrations (15.20±12.3 vs. 12.08±11.7; p=0.01) were significantly greater in female as compared to male newborns, respectively. Linear regression analysis indicated that umbilical cord leptin levels correlated with birth weight, umbilical triglyceride concentration, neonatal gender, and method of delivery.Conclusions: Our findings confirm the association of leptin concentrations with weight gain in fetal and newborn infants.

Association between FokI Polymorphism in Vitamin D Receptor Gene and Susceptibility to Spinal Tuberculosis in Chinese Han Population - Corrected Proof

2010-03-15

Background and Aims: Studies have shown that the vitamin D receptor (VDR) gene polymorphisms may be associated with pulmonary tuberculosis (TB) and play important roles in the regulation of calcium in a variety of tissues including bone. To our knowledge, however, whether FokI polymorphism in VDR gene is associated with susceptibility to spinal TB is still unknown. We undertook this study to investigate the association between FokI polymorphism in VDR gene and susceptibility to spinal TB in Chinese Han population.Methods: This study included 110 patients with spinal TB and 102 volunteers as controls. FokI polymorphism in VDR gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the spinal TB group and the control group. The frequencies of VDR-FokI genotypes in the two groups were compared using χ2 test.Results: There was a significant difference between groups in regard to the frequencies of the VDR-FokI genotypes (p <0.05). In the spinal TB group, the frequency of the ff genotype was 46.36%, which was significantly higher than the corresponding value for the control group (28.43%). Furthermore, the odds ratio (OR) was 2.176 (p <0.05), and the 95% confidence interval (CI) ranged from 1.236–3.832.Conclusions: FokI polymorphism in VDR gene may be associated with the susceptibility to spinal TB in Chinese Han population. Furthermore, the ff genotype may be the susceptible genotype of spinal TB.

Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Gastric Cancer: A Meta-analysis - Corrected Proof

Xingli Dong, Jianing Wu, Peng Liang, Jihong Li, Lijie Yuan, Xinghan Liu — 2010-03-15

Background and Aims: Case/control studies that investigated the association between gastric cancer and the MTHFR C677T and A1298C polymorphisms so far have provided controversial results. To clarify the effect of MTHFR polymorphisms on the risk of gastric cancer, a meta-analysis was performed.Methods: We performed a computerized search of the PubMed database for relevant reports before September 2009. No language restrictions were added. The associated literature was acquired through a deliberate retrieval strategy and selected based on the established inclusion criteria for publications.Results: The studies provided 4070/6462 cases/controls for C677T and 1923/3561 cases/controls for A1298C. There was significant heterogeneity (p = 0.015, I2 = 44.0%) among the 22 studies, and the RE model showed that the C677T allele T was associated with a 17.3% increased risk of gastric cancer compared with the allele C (RE OR = 1.173 [1.051–1.274]). Results from the subgroup analysis showed an increased risk in Asians (fixed-effect, FE OR 1.277 [1.179–1.382]), but not in Caucasians (random-effect, RE OR 1.194 [0.866–1.646]). The contrast of homozygotes (TT vs. CC) produced significant results in Asians (FE OR 1.611 [1.366–1.901]), whereas, in Caucasians, it was not significant (RE OR 1.385 [0.754–2.544]). In regard to the A1298C polymorphism, there was no heterogeneity among the 11 studies comparing the C vs. the A allele (p = 0.352, I2 = 9.7%), but no significant association was detected.Conclusions: The evidence from our meta-analysis supports that TT genotype of MTHFR C677T polymorphism contributes to susceptibility to gastric cancer, but no significant association was detected for CC genotype of MTHFR A1298C.

Lipoprotein Lipase Activity and Prediction for Survival in Lung Cancer - Corrected Proof

VIROJ WIWANITKIT — 2010-03-08

To the Editor: I read the recent publication by Trost et al. on lipoprotein lipase (LPL) activity in lung cancer with great interest . Trost et al. reached the conclusion that “Our study further underlines the involvement of cancer tissue LPL activity in tumor progression ”. Indeed, this result can be expected. The increased LDP activity in lung cancer is reported to be related to tumor growth. Recently, Cerne et al. noted that the higher LPL activity in lung cancer tissue provides a possible mechanism for increasing the supply of lipid nutrients to the tumor, necessary for tumor growth . However, there is no evidence for the further relationship between resulting tumor growth due to increased lipid nutrient and the patient survival. There is still a need for multivariate analysis to prove the exact relationship between LPL activity and survival in non-small cell lung cancer.

Reply: Increased Lipoprotein Lipase Activity in Non-small Lung Cancer Tissue Predicts Shorter Patient Survival - Corrected Proof

Darko Cerner — 2010-03-08

To the Editor: I found the analysis of our two papers very interesting. Close relationship between increased lipoprotein lipase (LPL) activity in non-small cell lung cancer tissue (compared to the adjacent noncancerous tissue) and shorter patient survival is intriguing and definitely needs further multivariate analysis. First, it would be interesting to evaluate the importance of LPL-driven influx of lipids to the tumor in relation to other mechanisms of lipids supply. External lipids could be supplied to the tumor also by several membrane receptors such as scavenger receptor class A (SR-A), LDL receptor and LDL receptor-related protein, to name only some of them. Furthermore, lipids can be synthesized intracellularly with fatty acid synthase. Here it is worth noting that the mechanisms for the lipids supply to the tumor must be studied concurrently because the deficit in one mechanism can easily be substituted by overexpression of the others. In addition to studying mechanisms for lipid supply, it should be determined whether the increased LPL activity and expression is a marker of some other not yet fully elucidated cellular and/or biochemical changes in the cancerous tissue that are essential for tumor growth. For instance, close relationship between LPL expression and SR-A1 expression, which we are observing constantly (data not shown), hints that increased LPL activity may signal the presence of tumor-associated macrophages, well-known contributors to tumor progression . Our study was designed as preliminary and with ongoing studies we are hoping to better characterize the underlying principle of the relationship between LPL activity in tumor and survival in non-small cell lung cancer.

Neurocysticercosis: Changes after 25 Years of Medical Therapy - Corrected Proof

Julio Sotelo, Claudia Diaz-Olavarrieta — 2010-03-08

Results of the first medical treatment for neurocysticercosis were published 25 years ago . At that time, this was the most frequent parasitic disease of the human brain . Until then the only therapeutic approach was neurosurgical extirpation of topographically accessible parasites. Since then, seminal reports have amply described the initial controversies over the benefits of cysticidal therapy , long-term effects on clinical signs , appearance of another medical treatment with albendazole that is more effective than praziquantel , pharmacological advances to reduce the initial doses and length of therapy (and consequently its costs) and controlled studies to delineate the best therapeutic scheme . Over the last 25 years, major scientific advances in cysticidal therapy have changed the entity, a millenary disease named by the Greeks from an ominous and expensive disease in former times to a far more favorable scenario nowadays.

Organization of a Third-level Care Hospital in Mexico City during the 2009 Influenza Epidemic - Corrected Proof

2010-01-29

An outbreak caused by the novel swine-origin influenza A (H1N1) virus was identified in Mexico in late March 2009. The objective of this report is to describe the organization of a tertiary care center in Mexico City during the contingency. We describe the education program, the hospital organization and triaging, and unforeseen overwhelming circumstances. Educational plans were directed to follow standard, contact, and droplet precautions and to condition behavior to avoid touching the eyes, nose, or mouth. N95 respirators were distributed only to perform respiratory procedures. By the fifth month into the epidemic, four patients with hospital-acquired influenza, 467 workers with respiratory symptoms suggestive of influenza (16% of our staff), and 96 workers with confirmed novel influenza A (3% of our staff) were identified. During the first 2 months of the epidemic, 44,225 people went through the triages and only 1503 (3.3%) reached the emergency room. By the fifth month into the epidemic, four small institutional influenza outbreaks (<10 workers each) had been identified, two of them in areas with no patient contact. Molecular testing for influenza was used mainly for epidemiological purposes. Even though we had a supply, we had difficulties in meeting the demand of masks, N-95 respirators, and hand sanitizers. Due to absenteeism, the nursing administration experienced difficulties in covering shifts. Preparation is mandatory for facing an influenza epidemic. The correct use of precautions is an economic measure to limit institutional transmission. Adequate triaging is essential to meet unusual attention demands.

What Have We Learned from the Novel Influenza A (H1N1) Pandemic in 2009 for Strengthening Pandemic Influenza Preparedness? - Corrected Proof

2010-01-29

We need to apply lessons learned from previous influenza pandemics to continuously update preparedness and response plans. It has become evident that strengthening networks of international referral laboratories coupled with scaling-up efforts to expand epidemiological surveillance networks is critical for responding and mitigating the impact of influenza pandemics. The current swine-related influenza A (H1N1) pandemic has also shown that international collaboration remains a critical component to effectively respond to influenza pandemics in the current globalized world.

Diagnostic Value of Adenosine Deaminase Activity in Benign and Malignant Breast Tumors - Corrected Proof

Mahmoud Aghaei, Fatemeh Karami-Tehrani, Siamak Salami, Morteza Atri — 2010-01-29

Background: The present study was carried out to evaluate the activity of adenosine deaminase (ADA) and its isoenzymes ADA1 and ADA2 activities as a diagnostic tool in patients with benign and malignant breast disease.Methods: Total ADA, ADA1, and ADA2 activities of serum and tumor were analyzed using 58 subjects including 20 patients with benign breast disease (BBD), 34 patients with primary breast cancer, and 20 patients as normal control subjects.Results: The mean values for total ADA and ADA2 activities in the serum and tumor of BBD were significantly higher than those of healthy controls (p <0.01). Furthermore, the mean values for total ADA and ADA2 activities of patients with breast cancer were significantly higher than those of the benign group (p <0.005) and healthy subjects (p <0.0001).Conclusions: Based on the present results, it is concluded that the assessment of total ADA and ADA2 activities may be used as a reliable test for differential diagnosis of benign and malignant breast disease.

Analysis of DNA Methylation Status of the Promoter of Human Telomerase Reverse Transcriptase in Gastric Carcinogenesis - Corrected Proof

Zhenghui Wang, Jinheng Xu, Xin Geng, Weiming Zhang — 2010-01-29

Background: Telomerase is expressed in normal somatic cells and reactivated in majority of tumor cells. Human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is a rate-limiting factor of telomerase activity. Evidence has shown that gastric cancer is the result of genetics and epignomics. DNA methylation is one of the most important research fields in epigenomics. It is one of the mechanisms resulting in gene silencing in carcinogenesis.Methods: Genomic DNAs were extracted from normal gastric mucosa, precancerous lesions and gastric cancer samples and were modified by sodium bisulfite. The modified genomic DNAs were amplified by PCR with primers that did not contain CpG sites. Each PCR product was sequenced. By matching the sequencing results and the original sequence, the status of each sample was obtained. PCR was carried out to identify hTERT expression.Results: The promoter of hTERT in gastric cancer was more methylated than in the precancerous lesions and normal gastric mucosa (p<0.05). hTERT was absent in normal gastric mucosa and its positive rate was higher in gastric cancer than in precancerous lesions (p<0.05).Conclusions: hTERT promoter in gastric cancer was more methylated than in the precancerous lesions and normal gastric mucosa. This may suggest that the degree of methylation of the hTERT promoter was increased during gastric carcinogenesis and may be a potential biological maker in early diagnosis of gastric cancer. During gastric carcinogenesis, expression of hTERT was increased. This may suggest that methylation of hTERT may influence expression of hTERT.

Taurine: A Potential Novel Addition to the Anti-Systemic Sclerosis Weaponry - Corrected Proof

Mohammad Kazem Fallahzadeh, Mohammad Reza Namazi, Ramesh C. Gupta — 2010-01-29

Vascular damage and immunological events leading to generation of fibrogenic fibroblasts are the main components of systemic sclerosis (SSc) pathogenesis. Superoxide anions play a role in endothelial damage by oxidizing circulating low-density lipoproteins. IL-1 plays a key role in the pathophysiology of SSc by inducing upregulation of adhesion molecules, inflammatory damage of the endothelium and tissue fibrosis. Elevated levels of proTh2 cytokines such as IL-6 in the early stages of SSc lead to enhanced fibroblast collagen production.Taurine, a semi-essential amino acid, is an antioxidant, inhibits the production of proinflammatory cytokines such as IL-1 and IL-6 and also inhibits production of TGF-β, a major fibrogenic cytokine.Therefore, we conclude that taurine may be a novel addition to the treatment armamentarium of this disabling disorder.

Comparison of the Pathology Caused by H1N1, H5N1, and H3N2 Influenza Viruses - Corrected Proof

Jeannette Guarner, Reynaldo Falcón-Escobedo — 2010-01-07

The spectrum of morbidity and mortality of H1N1, H5N1, and H3N2 influenza A viruses relates to the pathology they produce. In this review, we describe and compare the pathology of these viruses in human cases and animal models. The 1918 H1N1, the novel 2009 H1N1 pandemic virus, and H5N1 show inflammation, congestion, and epithelial necrosis of the larger airways (trachea, bronchi and bronchioles) with extension into the alveoli causing diffuse alveolar damage. Seasonal influenza A viruses (H3N2 and H1N1) have primarily caused inflammation, congestion and epithelial necrosis of the larger airways with lesser extension of the inflammatory process to alveoli. Localization of the inflammation and cellular damage relate to the presence of virus in different cell types. Infections with 1918 H1N1, the novel 2009 H1N1 pandemic virus, and H5N1 show virus in mucosal epithelial cells of the airways (from the nasopharynx to the bronchioles), alveolar macrophages, and pneumocytes, whereas infections with seasonal influenza viruses show viral antigens primarily in mucosal epithelial cells of the larger airways. The increased morbidity that has been encountered with the 2009 H1N1 virus is related to infection of cells in the upper and lower airways. The 2009 H1N1 virus shows similar pathology to that encountered with other highly virulent influenza A viruses such as the 1918 H1N1 and H5N1 viruses.

H1N1 Influenza Pandemics: Comparing the Events of 2009 in Mexico with those of 1976 and 1918–1919 - Corrected Proof

2010-01-07

Outbreaks of influenza A (H1N1) of avian- or swine-related origin have substantially impacted human populations. The most dramatic pandemic of influenza H1N1 occurred during 1918–1919 producing significant morbidity and mortality worldwide. In the 20th century, two other major pandemics took place but they were the H2N2 and H3N2 reassorted influenza strains. In 1976, a small outbreak of swine-related H1N1 in the U.S. led to a national scare but without any significant public health impact. More recently, in April 2009, in Mexico, and subsequently worldwide, an influenza (H1N1) triple reassortant strain produced >200,000 laboratory-confirmed cases and resulted in >2000 deaths. In August 2009, WHO declared this outbreak as the first influenza pandemic of the 21st century. It is critical to apply lessons learned during previous pandemics to mitigate the public health impact of the ongoing influenza pandemic in 2009. In particular, it is useful to compare the events in Mexico in 2009 to those during the Spanish influenza pandemic of 1918–1919.

Critical Analysis of Deaths Due to Atypical Pneumonia during the Onset of the Influenza A (H1N1) Virus Epidemic - Corrected Proof

2010-01-07

Background: The ongoing influenza A (H1N1) pandemic stroked Mexico and posed a huge challenge to the medical care and public health systems. This report analyzes the clinical course and process of care of patients who died due to atypical pneumonia and fulfilled the clinical criteria of suspected case of novel influenza A (H1N1) virus infection.Methods: We conducted a retrospective analysis of a series of 38 patients who died between April 7 and April 28, 2009 at Instituto Mexicano del Seguro Social (IMSS) hospitals due to severe pneumonia and respiratory distress. These cases coincided with the beginning of the outbreak, so patients did not undergo laboratory testing to diagnose influenza. According to IMSS and CDC criteria, post-hoc analysis allowed considering the presumptive diagnosis of S-OIV infection. A multidisciplinary group analyzed the information from the clinical charts, laboratory tests, radiographic studies and death certificates, using descriptive statistics.Results: Most cases were middle-aged (mean 33 years, range: 4–62 years) and previously healthy; 18.4% had an underlying chronic disease, 23.7% were obese and 7.9% were current smokers. None had received the seasonal influenza vaccine; they had cough (92%), fever (86.8%), and malaise (73.7%). The median time from disease onset to hospital admission was 6 days (range 0–8 days). All were admitted to the intensive care unit with pneumonia and/or respiratory distress. Average time from disease onset to death was 8 days (range 4–18 days).Conclusions: An increased number of severe cases of atypical pneumonia in previously healthy adults highlight the importance of the availability of a timely surveillance system able to identify sudden increases in the number of cases or presentation of apparently known diseases.