From anatomy to angioscopy: 164 years of crocodilian cardiovascular research, recent advances, and speculations

This paper present: a synthesis of current research on the crocodilian cardiovascular system with a view to encourage discussion and debate about the intricacies of this unique system and to provide ideas and suggestions for future studies. Innovative experimental approaches combined with new technologies have helped to resolve the complex flow and pressure patterns observed during non-shunting conditions that predominate in resting instrumented animals and during pulmonary to systemic shunting, which has been observed to occur spontaneously and during diving. The mechanisms and structures that may induce and regulate shunting are presented and the functional significance of a pulmonary to systemic shunt is discussed. (C) 1997 Elsevier Science Inc.

Clinical End Points and Response Criteria in Mycosis Fungoides and Sezary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

Mycosis fungoides (MF) and Sezary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin`s lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS. J Clin Oncol 29:2598-2607. (C) 2011 by American Society of Clinical Oncology

Risk Factors for Visual Field Progression in Treated Glaucoma

Objective: To determine intraocular pressure (IOP)-dependent and IOP-independent variables associated with visual field (VF) progression in treated glaucoma. Design: Retrospective cohort of the Glaucoma Progression Study. Methods: Consecutive, treated glaucoma patients with repeatable VF loss who had 8 or more VF examinations of either eye, using the Swedish Interactive Threshold Algorithm (24-2 SITA-Standard, Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc, Dublin, California), during the period between January 1999 and September 2009 were included. Visual field progression was evaluated using automated pointwise linear regression. Evaluated data included age, sex, race, central corneal thickness, baseline VF mean deviation, mean follow-up IOP, peak IOP, IOP fluctuation, a detected disc hemorrhage, and presence of beta-zone parapapillary atrophy. Results: We selected 587 eyes of 587 patients (mean [SD] age, 64.9 [13.0] years). The mean (SD) number of VFs was 11.1 (3.0), spanning a mean (SD) of 6.4 (1.7) years. In the univariable model, older age (odds ratio [OR], 1.19 per decade; P = .01), baseline diagnosis of exfoliation syndrome (OR, 1.79; P = .01), decreased central corneal thickness (OR, 1.38 per 40 mu m thinner; P < .01), a detected disc hemorrhage (OR, 2.31; P < .01), presence of beta-zone parapapillary atrophy (OR, 2.17; P < .01), and all IOP parameters (mean follow-up, peak, and fluctuation; P < .01) were associated with increased risk of VF progression. In the multivariable model, peak IOP (OR, 1.13; P < .01), thinner central corneal thickness (OR, 1.45 per 40 mu m thinner; P < .01), a detected disc hemorrhage (OR, 2.59; P < .01), and presence of beta-zone parapapillary atrophy (OR, 2.38; P < .01) were associated with VF progression. Conclusions: IOP-dependent and IOP-independent risk factors affect disease progression in treated glaucoma. Peak IOP is a better predictor of progression than is IOP mean or fluctuation.

DNA polymorphisms as tools for spinal cord injury research

Study Design: Data mining of single nucleotide polymorphisms (SNPs) in gene pathways related to spinal cord injury (SCI). Objectives: To identify gene polymorphisms putatively implicated with neuronal damage evolution pathways, potentially useful to SCI study. Setting: Departments of Psychiatry and Orthopedics, Faculdade de Medicina, Universidade de Sao Paulo, Brazil. Methods: Genes involved with processes related to SCI, such as apoptosis, inflammatory response, axonogenesis, peripheral nervous system development and axon ensheathment, were determined by evaluating the `Biological Process` annotation of Gene Ontology (GO). Each gene of these pathways was mapped using MapViewer, and gene coordinates were used to identify their polymorphisms in the SNP database. As a proof of concept, the frequency of subset of SNPs, located in four genes (ALOX12, APOE, BDNF and NINJ1) was evaluated in the DNA of a group of 28 SCI patients and 38 individuals with no SC lesions. Results: We could identify a total of 95 276 SNPs in a set of 588 genes associated with the selected GO terms, including 3912 nucleotide alterations located in coding regions of genes. The five non-synonymous SNPs genotyped in our small group of patients, showed a significant frequency, reinforcing their potential use for the investigation of SCI evolution. Conclusion: Despite the importance of SNPs in many aspects of gene expression and protein activity, these gene alterations have not been explored in SCI research. Here we describe a set of potentially useful SNPs, some of which could underlie the genetic mechanisms involved in the post trauma spinal cord damage.

Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case-control study

Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited. We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37-30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72-16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use. In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.

Variation in Body Composition Determines Long-Term Blood Pressure Changes in Pre-Hypertension The MONICA/KORA (Monitoring Trends and Determinants on Cardiovascular Diseases/Cooperative Research in the Region of Augsburg) Cohort Study

Objectives We studied the relationship between changes in body composition and changes in blood pressure levels. Background The mechanisms underlying the frequently observed progression from pre-hypertension to hypertension are poorly understood. Methods We examined 1,145 subjects from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. First, we studied individuals pre-hypertensive at baseline who, during 10 years of follow-up, either had normalized blood pressure (PreNorm, n = 48), persistently had pre-hypertension (PrePre, n = 134), or showed progression to hypertension (PreHyp, n = 183). In parallel, we studied predictors for changes in blood pressure category in individuals hypertensive at baseline (n = 429). Results After 10 years, the PreHyp group was characterized by a marked increase in body weight (+5.71% [95% confidence interval (CI): 4.60% to 6.83%]) that was largely the result of an increase in fat mass (+17.8% [95% CI: 14.5% to 21.0%]). In the PrePre group, both the increases in body weight (+1.95% [95% CI: 0.68% to 3.22%]) and fat mass (+8.09% [95% CI: 4.42% to 11.7%]) were significantly less pronounced than in the PreHyp group (p < 0.001 for both). The PreNorm group showed no significant change in body weight (-1.55% [95% CI: -3.70% to 0.61%]) and fat mass (+0.20% [95% CI: -6.13% to 6.52%], p < 0.05 for both, vs. the PrePre group). Conclusions After 10 years of follow-up, hypertension developed in 50.1% of individuals with pre-hypertension and only 6.76% went from hypertensive to pre-hypertensive blood pressure levels. An increase in body weight and fat mass was a risk factor for the development of sustained hypertension, whereas a decrease was predictive of a decrease in blood pressure. (J Am Coll Cardiol 2010; 56: 65-76) (C) 2010 by the American College of Cardiology Foundation