Angiotensin-I-converting enzyme (ACE) insertion/deletion polymorphism in Mexican patients with coronary artery disease. Association with the disease but not with lipid levels

Angiotensin-I-converting enzyme (ACE) insertion/deletion (ID) polymorphism has been associated with the genetic susceptibility to coronary artery disease (CAD) and also with the lipid profile in several populations. In the present work, we analyzed the distribution of ID polymorphism in 147 Mexican patients with CAD and 100 unrelated healthy controls. The correlation of this polymorphism with the lipid profile (cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides) in the patients group was determined. Increased frequency of D allele as well as DD genotype and decreased frequency of I allele and II genotype were found in CAD patients group (pC = 0.00058, OR = 1.96, pC = 0.021, OR = 2.5 and pC = 0.00058, OR = 0.51, pC = 0.0028, OR = 0.38). Correlation between ID genotypes and lipid profile in patients was carried out in total population and separately for females and males. After they had been adjusted for age, sex and BMI, there was no association among the three genotypes (II, ID and DD) and lipids and lipoproteins in none of the studied groups. Our data suggest that genetic variation at the ACE is a genetic factor related with the susceptibility to coronary artery disease in the Mexican Mestizo population.     

Serum levels of hypothalamic-pituitary-testicular axis hormones in men with or without prostate cancer or atypical small acinar proliferation

INTRODUCTION:

Substantial controversy exists regarding the association between testosterone serum levels and prostate cancer.

OBJECTIVE:

To evaluate the levels of hypothalamic‐pituitary‐testicular axis hormones in the sera of men with prostate cancer and atypical small acinar proliferation as well as those with normal biopsies.

METHODS:

A study cohort of 186 men with suspected prostate cancer who had undergone transrectal prostate biopsies was used in this study. The patients were divided into the following three groups based on the histology of the biopsy samples: no neoplasia, atypical small acinar proliferation or prostate cancer. Demographic data were also collected. Levels of total testosterone, follicle‐stimulating hormone, luteinizing hormone, prolactin, estradiol, and serum prostate‐specific antigen were measured in blood samples.

RESULTS:

Initially, 123 men were found to be without neoplasia, 26 with atypical small acinar proliferation and 37 with prostate cancer. After a second biopsy was taken from the men diagnosed with atypical small acinar proliferation, the diagnoses were revised: 18 were diagnosed with atypical small acinar proliferation and 45 with prostate cancer. No significant differences between the groups were identified regarding age, smoking history, chronic diseases, body mass index or PSA levels (P>0.05). The mean serum levels of testosterone, follicle‐stimulating hormone, luteinizing hormone, prolactin and estradiol were similar in all of the groups (P>0.05). Furthermore, in individuals with prostate cancer, the Gleason scores and prevalence of hypogonadism were not significantly different (P>0.05).

CONCLUSION:

The present study revealed no difference in the serum levels of testosterone, follicle‐stimulating hormone, luteinizing hormone, prolactin or estradiol in men without neoplasia compared with those with atypical small acinar proliferation or prostate cancer.     

Major basic protein from eosinophils and myeloperoxidase from neutrophils are required for protective immunity to Strongyloides stercoralis in mice

Eosinophils and neutrophils contribute to larval killing during the primary immune response, and neutrophils are effector cells in the secondary response to Strongyloides stercoralis in mice. The objective of this study was to determine the molecular mechanisms used by eosinophils and neutrophils to control infections with S. stercoralis. Using mice deficient in the eosinophil granule products major basic protein (MBP) and eosinophil peroxidase (EPO), it was determined that eosinophils kill the larvae through an MBP-dependent mechanism in the primary immune response if other effector cells are absent. Infecting PHIL mice, which are eosinophil deficient, with S. stercoralis resulted in development of primary and secondary immune responses that were similar to those of wild-type mice, suggesting that eosinophils are not an absolute requirement for larval killing or development of secondary immunity. Treating PHIL mice with a neutrophil-depleting antibody resulted in a significant impairment in larval killing. Naïve and immunized mice with neutrophils deficient in myeloperoxidase (MPO) infected with S. stercoralis had significantly decreased larval killing. It was concluded that there is redundancy in the primary immune response, with eosinophils killing the larvae through an MBP-dependent mechanism and neutrophils killing the worms through an MPO-dependent mechanism. Eosinophils are not required for the development or function of secondary immunity, but MPO from neutrophils is required for protective secondary immunity.     

Identification of a novel Tru9 I polymorphism in the human vitamin D receptor gene

We found a novel Tru9 I restriction polymorphism in intron 8 of the vitamin D receptor (VDR) gene in healthy French Caucasians. It corresponds to a substitution of A for G at nucleotide +443 bp from the end of exon 8. The allelic frequency of G and A in 151 unrelated subjects was 0.894 and 0.106, respectively. This polymorphism is located in the reverse primer binding site of primers that have been frequently used in the literature to genotype a BsmI restriction polymorphism. The presence of the Tru9I A allele may result in allele drop-out when the BsmI restriction fragment length polymorphism (RFLP) is genotyped with the original set of primers. This novel Tru9I polymorphism may be useful for analysis of the VDR gene. Received: August 2, 1999 / Accepted: September 21, 1999     

KIR genes and HLA class I ligands in a Caucasian Brazilian population with colorectal cancer

Colorectal cancer (CRC) can occur anywhere in the colon or rectum and represents the third most common cancer in the world in both sexes. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). The aim of our study was to evaluate the association between the KIR genes and HLA ligands in patients with colorectal cancer and healthy controls. We examined the polymorphism of 16 KIR genes and their HLA ligands in 154 caucasoid CRC patients and 216 controls. When both groups were compared, no significant differences were found for HLA ligands and KIR genes after Bonferroni correction. However, the Bx haplotypes (heterozygous and homozygous for the haplotype B) were more frequent in controls, when compared with patients. These findings suggest that individuals with Bx haplotypes could have some protection to colorectal cancer. The hypothesis is not related with the presence of a special KIR gene and HLA ligand related to the disease, but to the presence of several activating genes in the individuals with no better action of one in relation to other. Further studies to confirm this observation are warranted.     

Multi-dimensional Problems in Health Settings: A Review of Approaches to Decision Making

Introduction

There appears to be a growing number of prioritization exercises, for example of diseases, in health related settings (1). The decision process around these exercises involves comparing competing alternatives, i.e. diseases, and irreducible objectives. In addition to the multi-dimensional nature of the problem, the lack of reliable data, group dynamics associated to the involvement of experts, and the multiplicity of stakeholders, among other contextual factors, add complexity to the decision process. Here we review trends in such prioritization exercises and applications in different settings and for different events of interest, for example the management of emerging risks. Based on our findings, we discuss a conceptual framework based on multi-attribute utility theory presented to the World Organization for Animal Health (OIE) for the modification of its qualitative assessment of veterinary services performance into a quantifiable decision support system.

Methods

We searched PubMed for articles containing the key words ‘multi-criteria’, ‘multi-attribute’, ‘multi-objective’, ‘prioritization’, ‘decision making’ and their variations (e.g. without hyphenation) for the period 1990 to 2011 for human and veterinary medicine. We focused on prioritization methodologies and their sound application.

Results

A large number of prioritization efforts in health settings aim to produce a rank order of diseases to help allocation of scarce surveillance and disease control budgets. A number of applications target the prioritization of competing health interventions against specific diseases. Fewer target different events, for example emerging threats. Common mistakes found in multi-attribute prioritization approaches reported in the social sciences (2) appear also in public and animal health settings. In particular, the application of linear additive models to non-preferentially independent evaluation criteria, the poor design of attributes to assess the decision alternatives, the failure to define suitable criteria scales, and mistakes in defining trade-off weights were prevalent. In addition, most decision support tools tend to be overly complex. This not only compromises their acceptability and long-term sustainability but also increases the likelihood of methodological mistakes in their design and regular application. For example, the failure to properly identify and separate ‘ends’ objectives, such as the improvement of a country’s health, from ‘means’ objectives, i.e. required resources, in the definition of the fundamental drivers in any decision process.

Conclusions

Our findings, and experience in the practical application of formal prioritization methodologies (3), informed our advice to the OIE for the quantification of its tools for the assessment of veterinary services performance. The current framework used by the OIE produces a purely qualitative output with ordinal scales. The suggested quantitative extension allows additional outputs not available in their current form, for example, the aggregation of assessment scores at any level within the framework to produce a country’s overall score. It also permits the assessment of marginal performance improvements for every criterion and the consideration of trade-offs among the different criteria. The final output of our extension is the identification of the best portfolio of actions that will maximize the overall capability of national veterinary services given available resources. Quantification of the existing tool will deliver obvious benefits such as enhanced accountability and transparency in the decision making process, and will allow the historical analysis of a country’s veterinary services performance. The approach suggested to the OIE is adaptable to similar decision problems, such as monitoring the implementation of the International Health Regulations in a given country.     

Early-life environmental intervention may increase the number of neurons, astrocytes, and cellular proliferation in the hippocampus of rats

Neonatal handling reduces the stress response in adulthood due to a feedback mechanism. The present study analyzed the effects of repeated neonatal environmental intervention (daily handling during the first 10 days after birth) on neuron-, astroglial cell density, and cellular proliferation of the hippocampal (CA1, CA2, and CA3) pyramidal cell layers in female rats. Pups were divided into two groups, nonhandled and handled, which were submitted to repeated handling sessions between postnatal days 1 and 10. Histological and immunohistochemical procedures were used to determine changes in neuron density, astroglial cell density, and cellular proliferation. We found an increase in neuron density in each pyramidal cell layer of the hippocampus (CA1, CA2, and CA3) in female rats (11 and 90 day old) that were handled during the neonatal period. Furthermore, we found an increase in astroglial cell density in both hemispheres of the brain in the handled group. Finally, we observed an increase in cellular proliferation in both hippocampi (CA1, CA2, and CA3) of the brain in female pups (11 days old) handled during the neonatal period. This study demonstrates that an early-life environmental intervention may induce morphological changes in a structure involved with several functions, including the stress response. The results of the current study suggest that neonatal handling may influence the animals’ responses to environmental adversities later in life.     

Alternative transoral approach for intranasal tooth extraction

Intranasal ectopic eruption is an uncommon condition. Even if an intranasal tooth can be completely asymptomatic, sometimes a variety of nasal signs and symptoms may be associated, ranging from mild nasal congestion to recurrent epistaxis and purulent rhinorrhea. As a consequence, surgical removal is often required. Endoscopic extraction of the intranasal tooth has been reported to present several advantages with respect to traditional surgical approaches and thus recommended as routine treatment in such cases. However, when a tooth is impacted next to the nasal floor, an alternative approach could be needed. We suggest an alternative transoral approach to perform extraction of intranasal teeth, aimed at avoiding excessive bone removal to reach the nasal floor area and preventing the complications related to traditional intraoral buccal or palatal approach. It could represent a reliable alternative to traditional removal in the Oral Surgery Department.