Prognostic Value of Dobutamine Stress Echocardiography With Early Injection of Atropine With Versus Without Chronic Beta-Blocker Therapy in Patients With Known or Suspected Coronary Heart Disease

Although a new protocol of dobutamine stress echocardiography with the early injection of atropine (EA-DSE) has been demonstrated to be useful in reducing adverse effects and increasing the number of effective tests and to have similar accuracy for detecting coronary artery disease (CAD) compared with conventional protocols, no data exist regarding its ability to predict long-term events. The aim of this study was to determine the prognostic value of EA-DSE and the effects of the long-term use of beta blockers on it. A retrospective evaluation of 844 patients who underwent EA-DSE for known or suspected CAD was performed; 309 (37%) were receiving beta blockers. During a median follow-up period of 24 months, 102 events (12%) occurred. On univariate analysis, predictors of events were the ejection fraction (p <0.001), male gender (p <0.001), previous myocardial infarction (p <0.001), angiotensin-converting enzyme inhibitor therapy (p = 0.021), calcium channel blocker therapy (p = 0.034), and abnormal results on EA-DSE (p <0.001). On multivariate analysis, the independent predictors of events were male gender (relative risk [RR] 1.78, 95% confidence interval [CI] 1.13 to 2.81, p = 0.013) and abnormal results on EA-DSE (RR 4.45, 95% CI 2.84 to 7.01, p <0.0001). Normal results on EA-DSE with P blockers were associated with a nonsignificant higher incidence of events than normal results on EA-DSE without beta blockers (RR 1.29, 95% CI 0.58 to 2.87, p = 0.54). Abnormal results on EA-DSE with beta blockers had an RR of 4.97 (95% CI 2.79 to 8.87, p <0.001) compared with normal results, while abnormal results on EA-DSE without beta blockers had an RR of 5.96 (95% CI 3.41 to 10.44, p <0.001) for events, with no difference between groups (p = 0.36). In conclusion, the detection of fixed or inducible wall motion abnormalities during EA-DSE was an independent predictor of long-term events in patients with known or suspected CAD. The prognostic value of EA-DSE was not affected by the long-term use of beta blockers. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1291-1295)

The response of native Australian rodents to predator odours varies seasonally: a by-product of life history variation?

Small mammals are subject to predation from mammalian, avian and reptilian predators. There is an obvious advantage for prey species to detect the presence of predators in their environment, enabling them to make decisions about movement and foraging behaviour based on perceived risk of predation. We examined the effect of faecal odours from marsupial and eutherian predators, and a native reptilian predator, on the behaviour of three endemic Australian rodent species (the fawn-footed melomys, Melomys cervinipes, the bush rat, Rattus fuscipes, and the giant white-tailed rat, Uromys caudimaculatus) in rainforest remnants on the Atherton Tableland, North Queensland, Australia. Infrared camera traps were used to assess visit rates of rodents to odour stations containing faecal and control odours. Rodents avoided odour stations containing predator faeces, but did not avoid herbivore or control odours. The responses of the three prey species differed: in the late wet season U. caudimaculatus avoided predator odours, whereas R. fuscipes and M. cervinipes did not. In contrast, in the late dry season all three species avoided odour stations containing predator odours. We speculate that these different responses may result from variation in life history traits between the species. (c) 2006 The Association for the Study of Animal Behaviour Published by Elsevier Ltd. All rights reserved.

Results of high dose-rate brachytherapy boost before 2D or 3D external beam irradiation for prostate cancer

Background and purpose: To evaluate biochemical control and treatment related toxicity of patients with localized adenocarcinoma of the prostate treated with high dose-rate brachytherapy (HDRB) combined with conventional 2D or 3D-conformal external beam irradiation (EBI). Material and methods: Four-hundred and three patients treated between December 2000 and March 2004. HDRB was delivered with three fractions of 5.5-7 Gy with a single implant, followed by 45 Gy delivered with 2D or 3D conformal EBI. Results: The median follow-up was 48.4 months. Biochemical failure (BF) occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. Mean time to relapse was 13 and 26 months, respectively. The 5-year BF free survival using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively; using Phoenix criteria, 92.4%, 88.0% and 85.3%, respectively. The only predictive factor of BF in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules detected by digital palpation, and patients younger than 60 years presented a higher chance of failure using Phoenix criteria only. Conclusions: Treatment scheme is feasible and safe with good efficacy. (C) 2011 Elsevier Ireland Ltd All rights reserved. Radiotherapy and Oncology 98 (2011) 169-174

Coronary Artery Stenoses: Accuracy of 64-Detector Row CT Angiography in Segments with Mild, Moderate, or Severe Calcification-A Subanalysis of the CORE-64 Trial

Purpose: To evaluate the influence of cross-sectional arc calcification on the diagnostic accuracy of computed tomography (CT) angiography compared with conventional coronary angiography for the detection of obstructive coronary artery disease (CAD). Materials and Methods: Institutional Review Board approval and written informed consent were obtained from all centers and participants for this HIPAA-compliant study. Overall, 4511 segments from 371 symptomatic patients (279 men, 92 women; median age, 61 years [interquartile range, 53-67 years]) with clinical suspicion of CAD from the CORE-64 multi-center study were included in the analysis. Two independent blinded observers evaluated the percentage of diameter stenosis and the circumferential extent of calcium (arc calcium). The accuracy of quantitative multidetector CT angiography to depict substantial (>50%) stenoses was assessed by using quantitative coronary angiography (QCA). Cross-sectional arc calcium was rated on a segment level as follows: noncalcified or mild (<90 degrees), moderate (90 degrees-180 degrees), or severe (>180 degrees) calcification. Univariable and multivariable logistic regression, receiver operation characteristic curve, and clustering methods were used for statistical analyses. Results: A total of 1099 segments had mild calcification, 503 had moderate calcification, 338 had severe calcification, and 2571 segments were noncalcified. Calcified segments were highly associated (P < .001) with disagreement between CTA and QCA in multivariable analysis after controlling for sex, age, heart rate, and image quality. The prevalence of CAD was 5.4% in noncalcified segments, 15.0% in mildly calcified segments, 27.0% in moderately calcified segments, and 43.0% in severely calcified segments. A significant difference was found in area under the receiver operating characteristic curves (noncalcified: 0.86, mildly calcified: 0.85, moderately calcified: 0.82, severely calcified: 0.81; P < .05). Conclusion: In a symptomatic patient population, segment-based coronary artery calcification significantly decreased agreement between multidetector CT angiography and QCA to detect a coronary stenosis of at least 50%.

Comparison of reading performance after bilateral implantation of multifocal intraocular lenses with+3.00 or+4.00 diopter addition

PURPOSE To compare reading ability after cataract surgery and bilateral implantation of multifocal intraocular lenses (IOLs) with a +3 00 diopter (D) addition (add) or a +4 00 D add SETTING Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil DESIGN Prospective comparative study METHODS Patients scheduled for cataract surgery were randomly assigned to bilateral implantation of an aspheric AcrySof ReSTOR multifocal IOL with a +3 00 diopter (D) addition (add) or a +4 00 D add The reading speed, critical print size, and reading acuity were measured binocularly with best correction using MNREAD acuity charts 6 months after surgery Patients were tested with the chart at the best patient-preferred reading distance and at 40 cm Binocular uncorrected and best distance-corrected visual acuities at far and near were also measured RESULTS The study enrolled 32 patients At the best reading distance the results were similar between the 2 IOL groups in all reading parameters When tested at 40 cm, reading speed at all print sizes from 03 to 00 (all P< 001), critical print size (P< 001) and reading acuity (P = 014) were statistically significantly better in the +3 00 D IOL group than in the +4 00 DIOL group Uncorrected and corrected visual acuities at far and near were similar between the 2 groups CONCLUSION Although the 2 IOL groups had similar performance in reading parameters, patients had to adjust to their best reading distance The +3 00 D IOL performed better than the +4 00 D IOL at 40 cm

Lipid goals among patients with diabetes or metabolic syndrome: Lipid Treatment Assessment Project (L-TAP) 2

Objective: This analysis of the Lipid Treatment Assessment Project 2 population compared lipid goal attainment by diabetes and metabolic syndrome status. Research design and methods: Dyslipidaemic patients aged >= 20 years on stable lipid lowering therapy had their lipid levels determined once during enrolment at investigation sites in nine countries between September 2006 and April 2007. Achievement of low-density lipoprotein (LDL) cholesterol success, triglycerides < 150 mg/dl (1.7 mmol/l), and high-density lipoprotein (HDL) cholesterol success (> 40 mg/dl [1.0 mmol/l] in men or > 50 mg/dl [1.3 mmol/l] in women) was compared using logistic regression. Results: A total of 9955 patients were evaluated. Patients with diabetes, compared with those without diabetes, had lower achievement of LDL cholesterol goals (according to National Cholesterol Education Program Adult Treatment Panel [NCEP ATP] III guidelines; 67% vs. 75%), triglycerides < 150 mg/dl (55% vs. 64%), and HDL cholesterol success (61% vs. 74%; p < 0.0001 for all comparisons). The significantly lower lipid goal attainment in patients with diabetes was consistent across participating world regions. Patients with metabolic syndrome, compared with those without metabolic syndrome, had lower achievement of NCEP ATP III LDL cholesterol goals (69% vs. 76%), triglycerides < 150 mg/dl (36% vs. 83%), and HDL cholesterol success (49% vs. 89%; p < 0.0001 for all comparisons). As the number of metabolic syndrome components increased, lipid success rates progressively decreased (p < 0.0001 for LDL cholesterol success, triglycerides < 150 mg/dl, and HDL cholesterol success). Conclusions: This analysis indicates that despite their increased cardiovascular risk, patients with diabetes or metabolic syndrome remain undertreated.

Acute care surgeon South American model

Background In the World Health Organization book by Murray and Lopez (The Global Burden of Disease), the authors make the point that there are major regional differences across the world for death from injury. In the European market economies, injuries accounted for 6% of all deaths, of which the majority were the result of road traffic accidents. In stark contrast, in Latin America and the Caribbean, injuries account for 12-13% of all deaths, and most of these are the result of violence. An estimated 30% of all male deaths are from external causes, and road traffic accidents are the number two cause of death. Within South American countries, trauma is the second most common cause of death in Columbia, Venezuela, Ecuador, and Brazil. In other South American countries, it is the third or fourth most common cause of death. If one examines the Disability Adjusted Life Years, South America is the third highest in the world. Death from injury primarily affects people in the middle- and low-income group. Traffic accidents and suicide are the main causes of trauma in the high-income population. South America is made up of developing and poor countries that have trauma as a very important cause of death and disability. Methods The author has reviewed information on injury from the World Health Organization, Pan American Health Organization, and Brazilian Health Ministry. In addition, a search of injury was performed through MEDLINE. Results and Conclusions The results of this review show that trauma is a major public health problem in South America. At the present time, there is a lack of statewide system development. In addition, there are difficulties in training surgeons to cope with these problems.

Genetic Contribution for Non-Syndromic Cleft Lip With or Without Cleft Palate (NS CL/P) in Different Regions of Brazil and Implications for Association Studies

Non-syndromic cleft lip with or without cleft palate (NS CL/P) is a complex disease in which heritability estimates vary widely depending on the population studied. To evaluate the importance of genetic contribution to NS CL/P in the Brazilian population, we conducted a study with 1,042 families from five different locations (Santarem, Fortaleza, Barbalha, Maceio, and Rio de Janeiro). We also evaluated the role of consanguinity and ethnic background. The proportion of familial cases varied significantly across locations, with the highest values found in Santarem (44%) and the lowest in Maceio (23%). Heritability estimates showed a higher genetic contribution to NS CL/P in Barbalha (85%), followed by Santarem (71%), Rio de Janeiro (70%), Fortaleza (64%), and Maceio (45%). Ancestry was not correlated with the occurrence of NS CL/P or with the variability in heritability. Only in Rio de Janeiro was the coefficient of inbreeding significantly larger in NS CL/P families than in the local population. Recurrence risk for the total sample was approximately 1.5-1.6%, varying according to the location studied (0.6-0.7% in Maceio to 2.2-2.8% in Barbalha). Our findings show that the degree of genetic contribution to NS CL/P varies according to the geographic region studied, and this difference cannot be attributed to consanguinity or ancestry. These findings suggest that Barbalha is a promising region for genetic studies. The data presented here will be useful in interpreting results from molecular analyses and show that care must be taken when pooling samples from different populations for association studies. (C) 2011 Wiley-Liss, Inc.

Fluid Resuscitation With Isotonic or Hypertonic Saline Solution Avoids Intraneural Calcium Influx After Traumatic Brain Injury Associated With Hemorrhagic Shock

Background: Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Methods: Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer`s, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion (""clinical penumbra"") and from the corresponding contralateral side (""lesion`s mirror"") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Results: Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Conclusion: Both small volume hypertonic saline and large volume lactated Ringer`s blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Expression of resistance by tetraploid and diploid lucerne genotypes to Phytophthora medicaginis is not influenced by inoculum level or by temperature

Phytophthora-resistant lucerne cultivars do not always perform well under conditions of high disease pressure in the field. To determine whether resistance expression remains stable under different infection intensities, tetraploid and diploid lucerne genotypes, genotypically defined for their reactions to Phytophthora medicaginis, were clonally propagated, and the influence of different reproducible inoculum levels (0 . 5 and 5 . 0 g dry weight mycelium/kg dry weight potting mix), the period of exposure to these levels (10-60 days), and temperature (16/22 degrees C and 24/30 degrees C) on disease expression was determined in controlled environments. Generally, expression of resistance by resistant genotypes, remained stable under these conditions. Biotic (e.g. Aphanomyces eutiches) or abiotic factors other than P. medicaginis may be responsible for the poorer than expected performance under field conditions in some instances, or the percentage of resistant plants in some cultivars currently classified as resistant is insufficient to provide buffering against productivity reductions under severe epidemics. Further research is needed to clarify the situation.

Crystal structure of Escherichia coli xanthine phosphoribosyltransferase

Xanthine phosphoribosyltransferase (XPRT; EC 2.4.2.22) from Escherichia coil is a tetrameric enzyme having 152 residues per subunit. XPRT catalyzes the transfer of the phosphoribosyl group from 5-phospho-alpha-D-ribosyl l-pyrophosphate (PRib-PP) to the 6-oxopurine bases guanine, xanthine, and hypoxanthine to form GMP, XMP, and IMP, respectively. Crystals grown in the absence of substrate or product were used to determine the structure of XPRT at a resolution of 1.8 Angstrom by multiple isomorphous replacement. The core structure of XPRT includes a five-stranded parallel B-sheet surrounded by three or-helices, which is similar to that observed in other known phosphoribosyltransferase (PRTase) structures. The XPRT structure also has several interesting features. A glutamine residue in the purine binding site may be responsible for the altered 6-oxopurine base specificity seen in this enzyme compared to other 6-oxopurine PRTases. Also, we observe both a magnesium ion and a sulfate ion bound at the PRib-PP binding site of XPRT. The sulfate ion interacts with Arg-37 which has a cis-peptide conformation, and the magnesium ion interacts with Asp-89, a highly conserved acidic residue in the PRib-PP binding site motif. The XPRT structure also incorporates a feature which has not been observed in other PRTase structures. The C-terminal 12 residues of XPRT adopt an unusual extended conformation and make interactions with a neighboring subunit. The very last residue, Arg-152, could form part of the active site of a symmetry-related subunit in the XPRT tetramer.

Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system

A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy, Blood pressure, heart rate, fetuses and dams` body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the US group than in the NS and HS groups. The PRA was greater in IS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of angiotensins I and II were lower in the HS group than in the ISIS and IS groups. Placental angiotensin receptor type 1 (AT(1)) gene expression and levels of thiobarbituric acid reactive substances (TBARS) were higher in HS dams, as were uterine blood flow and cardiac output. The degree of salt intake did not influence plasma sodium, potassium or creatinine. Although fractional sodium excretion was higher in HS dams than in NS and LS dams, fractional potassium excretion was unchanged. In conclusion, findings from this study indicate that the reduction in fetal weight in response to salt restriction during pregnancy does not involve alterations in uterine-placental perfusion or the RAS. Moreover, no change in fetal weight is observed in response to salt overload during pregnancy. However, salt overload did lead to an increase in placental weight and uterine blood flow associated with alterations in maternal plasma and placental RAS. Therefore, these findings indicate that changes in salt intake during pregnancy lead to alterations in uterine-placental perfusion and fetal growth. (C) 2008 Elsevier Inc. All rights reserved.

Cardiovascular, metabolic and hormonal responses to the progressive exercise performed to exhaustion in patients with type 2 diabetes treated with metformin or glyburide

Objectives: To evaluate the effects of Metformin and Glyburide on cardiovascular, metabolic and hormonal parameters during progressive exercise performed to exhaustion in the post-prandial state in women with type 2 diabetes (T2DM). Design and Methods: Ten T2DM patients treated with Metformin (M group), 10 with Glyburide (G group) and 10 age-paired healthy subjects exercised on a bicycle ergometer up to exercise peak. Cardiovascular and blood metabolic and hormonal parameters were measured at times -60 min, 0 min, exercise end, and at 10 and 20 minutes of recovery phase. Thirty minutes before the exercise, a standard breakfast was provided to all participants. The diabetic patients took Metformin or Glyburide before or with meal. Results: Peak oxygen uptake (VO2) was lower in patients with diabetes. Plasma glucose levels remained unchanged, but were higher in both diabetic groups. Patients with diabetes also presented lower insulin levels after meals and higher glucagon levels at exercise peak than C group. Serum cortisol levels were higher in G than M group at exercise end and recovery phase. Lactate levels were higher in M than G group at fasting and in C group at exercise peak. Nor epinephrine, GH and FFA responses were similar in all 3 groups. Conclusion: Progressive exercise performed to exhaustion, in the post-prandial state did not worsen glucose control during and after exercise. The administration of the usual dose of Glyburide or Metformin to T2DM patients did not influence the cardiovascular, metabolic and hormonal response to exercise.