Ergospirometry and Echocardiography in Early Stage of Heart Failure with Preserved Ejection Fraction and in Healthy Individuals

AbstractBackground:Heart failure with preserved ejection fraction is a syndrome characterized by changes in diastolic function; it is more prevalent among the elderly, women, and individuals with systemic hypertension (SH) and diabetes mellitus. However, in its early stages, there are no signs of congestion and it is identified in tests by adverse remodeling, decreased exercise capacity and diastolic dysfunction.Objective:To compare doppler, echocardiographic (Echo), and cardiopulmonary exercise test (CPET) variables - ergospirometry variables - between two population samples: one of individuals in the early stage of this syndrome, and the other of healthy individuals.Methods:Twenty eight outpatients diagnosed with heart failure according to Framingham’s criteria, ejection fraction > 50% and diastolic dysfunction according to the european society of cardiology (ESC), and 24 healthy individuals underwent Echo and CPET.Results:The group of patients showed indexed atrial volume and left ventricular mass as well as E/E’ and ILAV/A´ ratios significantly higher, in addition to a significant reduction in peak oxygen consumption and increased VE/VCO2 slope, even having similar left ventricular sizes in comparison to those of the sample of healthy individuals.Conclusion:There are significant differences between the structural and functional variables analyzed by Echo and CPET when comparing two population samples: one of patients in the early stage of heart failure with ejection fraction greater than or equal to 50% and another of healthy individuals.

Effects of foliar fertilization of common bean (Phaseolus vulgaris, L.) during the seed-filling stage

An experiment was carried out with common bean (Phaseolus vulgaris, L.) in a Red Yellow Latossol, sandy phase, in order to study the influence of foliar spraying of the Hanway nutrient solution (NPKS) at grain filling stage on: 1) grain yield; 2) the uptake of fertilizer and soil nitrogen by this crop through the root system and 3) the efficiency of utilization of the nitrogen in the foliar spray solution by the grain. The results of this experiment showed that the foliar application of the Hanway solution with ammonium nitrate at the pod filling period caused severe leaf burn and grain yield was inferior to that of the plants which received a soil application of this fertilizer at the same stage. These facts can be attributed to the presence of ammonium nitrate in the concentration used. The composition of final spray was: 114,28 Kg NH4NO3 + 43,11 Kg potassium poliphosphate + 12,44 Kg potassium sulphate per 500 litres. The uptake of nitrogen fertilizer through the root system and the efficiency of its utilization was greater than that through the leaves.

Alterações cutâneas do cão no Kala-Azar sul-americano

According to E. Chagas (1938), South-American Kala Azar is a widespread disease from the jungle, several cases being reported from North Brazil (Estado do Pará: Marajó Island, Tocantins and Gurupi river valleys; Estados do Piauí and Ceará: coast and hinterland). Other cases were found in Northeast Brazil (Estados de Pernambuco, Alagôas and Sergipe: coast and hinterland; Estado da Bahia: hinterland). A few cases were described from Estado de Mato-Grosso (Brazil), Provincia de Salta and Território do Chaco (Argentine), and Zona contestada do Chaco (Paraguai-Bolívia). A well defined secondary anemia associated with enlargement of the liver and spleen are the chief symptoms. Death usually occurs in cachexia and with symptoms of heart failure. Half the patients were children aged less than ten years (CHAGAS, CASTRO & FERREIRA, 1937). Quite exhaustive epidemiological researches performed by CHAGAS, FERREIRA, DEANE, DEANE & GUIMARÃES (1938) in Municipio de Abaeté (Estado do Pará, Brazil) gave the incidence of 1.48% for the natural infection in human, 4.49% in dogs, and 2.63% in cats. The infection was arcribed (CUNHA & CHAGAS, 1937) to a new species of Leishmania (L. chagasi). Latter CUNHA (1938) state, that it is identical to L. infantum. ADLER (1940) found that so far it has been impossible to distinguish L. chagasi from L. infantum by any laboratory test but a final judgment must be reserved until further experiments with different species of sandflies have been carried out. Skin changes in canine Kala Azar were signaled by many workers, and their importance as regards the transmission of the disease is recognized by some of them (ADLER & THEODOR, 1931, 2. CUNHA, 1933). Cutaneous ulcers in naturally infected dogs are referred by CRITIEN (1911) in Malta, by CHODUKIN & SCHEVTSCHENKO (1928) in Taschkent, by DONATIEN & LESTOCQUARD (1929) and by LESTOCQUARD & PARROT (1929) in Algeria, and by BLANC & CAMINOPETROS (1931) in Greece. Depilation is signaled by YAKIMOFF & KOHL-YAKIMOFF (1911) in Tunis, by YAKIMOFF (1915) in Turkestan. Eczematous areas or a condition described as "eczema furfurace" is sometimes noted in the areas of depilation (DONATIEN & LESTOCQUARD). The skin changes noticed by ADLER & THEODOR (1932) in dogs naturally infected with Mediterranean Kala Azar can be briefly summarized as a selective infiltration of macrophages around hair follicles including the sebaceous glands and the presence of infected macrophages in normal dermis. The latter phenomenon in the complete absence of secondary infiltration of round cells and plasma cells is the most striking characteristic of canine Kala Azar and differentiates it from L. tropica. In the more advanced stages the dermis is more cellular than that of normal dogs and may even contain a few small dense areas of infiltration with macrophages and some round cells and polymorphs. The external changes, i. e., seborrhea and depilation are roughly proportional to the number of affected hair follicles. In dogs experimentally infected with South-American Kala Azar the parasites were regularly found in blocks of skin removed from the living animal every fortnight (CUNHA, 1938). The changes noticed by CUNHA, besides the presence of Leishmania, were perivascular and diffuse infiltration of the cutis with mononuclears sometimes more marked near hair follicles, as well as depilation, seborrhea and ulceration. The parasites were first discovered and very numerous in the paws. Our material was obtained from dogs experimentally infected by Dr. A. MARQUES DA CUNHA< and they were the subject of a previous paper by CUNHA (1938). In this study, however, several animals were discarded as it was found that they did develop a superimposed infection by Demodex canis. This paper deals with the changes found in 88 blocks of skin removed from five dogs, two infected with two different canine strains, and three with two distinct human strains of South-American Kala Azar. CUNHA'S valuable material affords serial observations of the cutaneous changes in Kala Azar as most of the blocks of skin were taken every fortnight. The following conclusions were drawn after a careful microscopic study. (1) Skin changes directly induced in the dog by the parasites of South-American Kala Azar may b described as an infiltration of the corium (pars papillaris and upper portion of the reticular layer) by histocytes. Parasites are scanty, at first, latter becoming very numerous in the cytoplasm of such cells. Sometimes the histocytes either embedding or not leishman bodies appear as distinct nodes of infiltration or cell aggregations (histocytic granuloma, Figs. 8 and 22) having a perivascular distribution. The capillary loops in the papillae, the vessels of the sweat glands, the subpapillary plexus, the vertical twigs connecting the superficial and deep plexuses are the ordinary seats of the histocytic Kala Azar granulomata. (2) Some of the cutaneous changes are transient, and show spontaneous tendency to heal. A gradual transformation of the histocytes either containing or not leishman bodies into fixed connective tissue cells or fibroblasts occut and accounts for the natural regression just mentioned. Figs. 3, 5, 18, 19 and 20 are good illustrations of such fibroblastic transformation of the histocytic Kala Azar granulomata. (3) Skin changes induced by the causative organism of South-American Kala Azar are neither uniform nor simultaneous. The same stage may be found in the same dog in different periods of the disease, and not the same changes take place when pieces from several regions are examined in the same moment. The fibroblastic transformation of the histocytic granulomata marking the beginning of the process of repair, e. g., was recognised in dog C, in the 196th as well as in the 213rd (Fig. 18) and 231st (Fig. 19) days after the inoculation. (4) The connective tissue of the skin in dogs experimentally infected with South-American Kala Azar is overflowed by blood cells (monocytes and lymphocytes) besides the proliferation in situ of undifferentiated mesenchymal cells. A marked increase in the number of cells specially the "ruhende Wanderzellen" (Figs. 4 and 15) is noticed even during the first weeks after inoculation (prodomal stage) when no leishman bodies are yet found in the skin. Latter a massive infiltration by amoeboid wandering cells similar to typical blood monocytes (Fig. 21) associated to a small number of lymphocytes and plasma cells (Figs. 9, 17, 21, and 24) indicates that the emigration of blood cells...

Nuclear factor I-C links platelet-derived growth factor and transforming growth factor beta1 signaling to skin wound healing progression.

Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.

New FFT/IFFT Factorizations with Regular Interconnection Pattern Stage-to-Stage Subblocks

Les factoritzacions de la FFT (Fast Fourier Transform) que presenten un patró d’interconnexió regular entre factors o etapes son conegudes com algorismes paral·lels, o algorismes de Pease, ja que foren originalment proposats per Pease. En aquesta contribució s’han desenvolupat noves factoritzacions amb blocs que presenten el patró d’interconnexió regular de Pease. S’ha mostrat com aquests blocs poden ser obtinguts a una escala prèviament seleccionada. Les noves factoritzacions per ambdues FFT i IFFT (Inverse FFT) tenen dues classes de factors: uns pocs factors del tipus Cooley-Tukey i els nous factors que proporcionen la mateix patró d’interconnexió de Pease en blocs. Per a una factorització donada, els blocs comparteixen dimensions, el patró d’interconnexió etapa a etapa i a més cada un d’ells pot ser calculat independentment dels altres.

Critical evaluation of outcome scales to assess outcome after lateral ankle ligament repair

Introduction: Several scores are commonly used to evaluate patients' postoperative satisfaction after lateral ankle ligament repair, including: AOFAS, FAAM, CAIT and CAIS. Comparing published studies in the literature is difficult, as the same patient can have markedly different results depending on which scoring system is used. The current study aims to address this gap in the literature by developing a system to compare these tests, to allow better analysis and comparison of published studies. Patients and methods: This is a retrospective cohort study of 47 patients following lateral ankle ligament repair using a modified Broström-Gould technique. All patients were operated between 2005 and 2010 by a single surgeon and followed the same post operative rehabilitation protocol. Six patients were excluded from the study because of concomitant surgery. Patients were assessed by an independent observer. We used the Pearson correlation coefficient to analyse the concordance of the scores, as well as scatter plots to assess the linear relationship between them. Results: A linear distribution between the scores was found when the results were analysed using scatter plots. We were thus able to use the Pearson correlation coefficient to evaluate the relationship between each of the different postoperative scores. The correlation was found to be above 0.5 in all cases except for the comparison between the CAIT and the FAAM for the activities of daily living (0.39). We were, therefore, able to compare the results obtained and assess the relative concordance of the scoring systems. The results showed that the more specific the scale is, the worst the score is and inversely. So the CAIT and the CAIS appeared to be more severe than the AOFAS and the FAAM measuring the activities of daily living. The sports subscale of the FAAM demonstrated intermediate results. Conclusion: This study outlines a system to compare different postoperative scores commonly used to evaluate outcome after ankle stabilization surgery. The impact of this study is that it makes comparison of published studies easier, even though they use a variety of different clinical scores, thus facilitating better outcome analysis of operative techniques.

A glycine-arginine domain in control of the human MRE11 DNA repair protein.

Human MRE11 is a key enzyme in DNA double-strand break repair and genome stability. Human MRE11 bears a glycine-arginine-rich (GAR) motif that is conserved among multicellular eukaryotic species. We investigated how this motif influences MRE11 function. Human MRE11 alone or a complex of MRE11, RAD50, and NBS1 (MRN) was methylated in insect cells, suggesting that this modification is conserved during evolution. We demonstrate that PRMT1 interacts with MRE11 but not with the MRN complex, suggesting that MRE11 arginine methylation occurs prior to the binding of NBS1 and RAD50. Moreover, the first six methylated arginines are essential for the regulation of MRE11 DNA binding and nuclease activity. The inhibition of arginine methylation leads to a reduction in MRE11 and RAD51 focus formation on a unique double-strand break in vivo. Furthermore, the MRE11-methylated GAR domain is sufficient for its targeting to DNA damage foci and colocalization with gamma-H2AX. These studies highlight an important role for the GAR domain in regulating MRE11 function at the biochemical and cellular levels during DNA double-strand break repair.

Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration?

Peripheral nerve injury is a serious problem affecting significantly patients' life. Autografts are the "gold standard" used to repair the injury gap, however, only 50% of patients fully recover from the trauma. Artificial conduits are a valid alternative to repairing peripheral nerve. They aim at confining the nerve environment throughout the regeneration process, and providing guidance to axon outgrowth. Biocompatible materials have been carefully designed to reduce inflammation and scar tissue formation, but modifications of the inner lumen are still required in order to optimise the scaffolds. Biomicking the native neural tissue with extracellular matrix fillers or coatings showed great promises in repairing longer gaps and extending cell survival. In addition, extracellular matrix molecules provide a platform to further bind growth factors that can be released in the system over time. Alternatively, conduit fillers can be used for cell transplantation at the injury site, reducing the lag time required for endogenous Schwann cells to proliferate and take part in the regeneration process. This review provides an overview on the importance of extracellular matrix molecules in peripheral nerve repair.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.