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...

Examples of retracts in a free group that are not the fixed subgroup of any group of automorphisms

Let F be a free group of rank at least three. We show that some retracts of F previously studied by Martino-Ventura are not equal to the fixed subgroup of any group of automorphisms of F. This shows that, in F, there exist subgroups that are equal to the fixed subgroup of some set of endomorphisms but are not equal to the fixed subgroup of any set of automorphisms. Moreover, we determine the Galois monoids of these retracts, where, by the Galois monoid of a subgroup H of F, we mean the monoid consisting of all endomorphisms of F that fix H.

Stable coalition structures with fixed decision scheme

This paper studies the stability of a finite local public goods economy in horizontal differentiation, where a jurisdiction's choice of the public good is given by an exogenous decision scheme. In this paper, we characterize the class of decision schemes that ensure the existence of an equilibrium with free mobility (that we call Tiebout equilibrium) for monotone distribution of players. This class contains all the decision schemes whose choice lies between the Rawlsian decision scheme and the median voter with mid-distance of the two median voters when there are ties. We show that for non-monotone distribution, there is no decision scheme that can ensure the stability of coalitions. In the last part of the paper, we prove the non-emptiness of the core of this coalition formation game

T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression.

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR.

Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Innovation sources and productivity in Catalonian firms: a quantile regression analysis

This paper explores the effects of two main sources of innovation -intramural and external R&D- on the productivity level in a sample of 3,267 Catalonian firms. The data set used is based on the official innovation survey of Catalonia which was a part of the Spanish sample of CIS4, covering the years 2002-2004. We compare empirical results by applying usual OLS and quantile regression techniques both in manufacturing and services industries. In quantile regression, results suggest different patterns at both innovation sources as we move across conditional quantiles. The elasticity of intramural R&D activities on productivity decreased when we move up the high productivity levels both in manufacturing and services sectors, while the effects of external R&D rise in high-technology industries but are more ambiguous in low-technology and knowledge-intensive services. JEL codes: O300, C100, O140. Keywords: Innovation sources, R&D, Productivity, Quantile regression

Proper actions, fixed-point algebras and naturality in nonabelian duality

"Vegeu el resum a l'incici del document del fitxer adjunt."

Detection of viral infection by immunofluorescence in formalin-fixed tissues, pretreated with trypsin

The presence of viral antigen in sections from formalin-fixed and paraffin-embedded human tissues was demonstrated by trypsin digestion followed by direct or indirect immunofluorescence. The specimens may be used for retrospective diagnosis. The immunofluorescence technique has to be adapted to the suspected virus infection on the basis of previous histopathology study. Variations of trypsin concentration time and temperature of incubation, expose different viral antigens and have to be previously tested for each unknown system. For measles virus detection in lung a stronger digestion has to be applied as compared to adenovirus or respiratory disease viruses in the same tisue. Flavivirus in liver tissue needs a weaker digestion. The reproducibility of the method makes it useful as a routine technique in diagnosis of virus infection.

A priori ratemaking using bivariate poisson regression models

In automobile insurance, it is useful to achieve a priori ratemaking by resorting to gene- ralized linear models, and here the Poisson regression model constitutes the most widely accepted basis. However, insurance companies distinguish between claims with or without bodily injuries, or claims with full or partial liability of the insured driver. This paper exa- mines an a priori ratemaking procedure when including two di®erent types of claim. When assuming independence between claim types, the premium can be obtained by summing the premiums for each type of guarantee and is dependent on the rating factors chosen. If the independence assumption is relaxed, then it is unclear as to how the tari® system might be a®ected. In order to answer this question, bivariate Poisson regression models, suitable for paired count data exhibiting correlation, are introduced. It is shown that the usual independence assumption is unrealistic here. These models are applied to an automobile insurance claims database containing 80,994 contracts belonging to a Spanish insurance company. Finally, the consequences for pure and loaded premiums when the independence assumption is relaxed by using a bivariate Poisson regression model are analysed.

Innovation sources and productivity: a quantile regression analysis

This paper explores the effects of two main sources of innovation —intramural and external R&D— on the productivity level in a sample of 3,267 Catalan firms. The data set used is based on the official innovation survey of Catalonia which was a part of the Spanish sample of CIS4, covering the years 2002-2004. We compare empirical results by applying usual OLS and quantile regression techniques both in manufacturing and services industries. In quantile regression, results suggest different patterns at both innovation sources as we move across conditional quantiles. The elasticity of intramural R&D activities on productivity decreased when we move up the high productivity levels both in manufacturing and services sectors, while the effects of external R&D rise in high-technology industries but are more ambiguous in low-technology and services industries.

Factors explaining local privatization: A meta-regression analysis

Privatization of local public services has been implemented worldwide in the last decades. Why local governments privatize has been the subject of much discussion, and many empirical works have been devoted to analyzing the factors that explain local privatization. Such works have found a great diversity of motivations, and the variation among reported empirical results is large. To investigate this diversity we undertake a meta-regression analysis of the factors explaining the decision to privatize local services. Overall, our results indicate that significant relationships are very dependent upon the characteristics of the studies. Indeed, fiscal stress and political considerations have been found to contribute to local privatization specially in the studies of US cases published in the eighties that consider a broad range of services. Studies that focus on one service capture more accurately the influence of scale economies on privatization. Finally, governments of small towns are more affected by fiscal stress, political considerations and economic efficiency, while ideology seems to play a major role for large cities.

Evaluating sampling strategies and logistic regression methods for modelling complex land cover changes

The role of land cover change as a significant component of global change has become increasingly recognized in recent decades. Large databases measuring land cover change, and the data which can potentially be used to explain the observed changes, are also becoming more commonly available. When developing statistical models to investigate observed changes, it is important to be aware that the chosen sampling strategy and modelling techniques can influence results. We present a comparison of three sampling strategies and two forms of grouped logistic regression models (multinomial and ordinal) in the investigation of patterns of successional change after agricultural land abandonment in Switzerland. Results indicated that both ordinal and nominal transitional change occurs in the landscape and that the use of different sampling regimes and modelling techniques as investigative tools yield different results. Synthesis and applications. Our multimodel inference identified successfully a set of consistently selected indicators of land cover change, which can be used to predict further change, including annual average temperature, the number of already overgrown neighbouring areas of land and distance to historically destructive avalanche sites. This allows for more reliable decision making and planning with respect to landscape management. Although both model approaches gave similar results, ordinal regression yielded more parsimonious models that identified the important predictors of land cover change more efficiently. Thus, this approach is favourable where land cover change pattern can be interpreted as an ordinal process. Otherwise, multinomial logistic regression is a viable alternative.

Bayesian Model Averaging in the Instrumental Variable Regression Model

This paper considers the instrumental variable regression model when there is uncertainty about the set of instruments, exogeneity restrictions, the validity of identifying restrictions and the set of exogenous regressors. This uncertainty can result in a huge number of models. To avoid statistical problems associated with standard model selection procedures, we develop a reversible jump Markov chain Monte Carlo algorithm that allows us to do Bayesian model averaging. The algorithm is very exible and can be easily adapted to analyze any of the di¤erent priors that have been proposed in the Bayesian instrumental variables literature. We show how to calculate the probability of any relevant restriction (e.g. the posterior probability that over-identifying restrictions hold) and discuss diagnostic checking using the posterior distribution of discrepancy vectors. We illustrate our methods in a returns-to-schooling application.