Mucocutaneous leishmaniasis must be included in the differential diagnosis of midline destructive disease: two case reports.

Midline destructive lesions have multiple possible etiologies, which can be grouped into neoplastic, infectious, or vasculitis-associated. The purpose of these case reports and literature review was to highlight the need to include mucocutaneous leishmaniasis in the diagnosis of midfacial lesions in any patient who has lived in Leishmania-endemic areas because this entity meets all of the clinical criteria to be considered a form of midline destructive lesion. We present two cases of mucocutaneous leishmaniasis that occurred in a Bolivian male immigrant and a European male traveler to Panama, in whom lesions were misdiagnosed as different midline destructive lesions with different causes (Wegener, vasculitis, and natural killer or T-cell lymphoma [NKTL]). The conclusion of our work is that all patients with midline destructive lesions should undergo histologic and molecular studies to be evaluated for mucosal leishmaniasis, particularly patients whose clinical history suggests this possibility. In cases of uvular involvement, biopsy of this region might be a possible alternative to nasal biopsy.

On species persistence-time distributions.

We present new theoretical and empirical results on the probability distributions of species persistence times in natural ecosystems. Persistence times, defined as the timespans occurring between species' colonization and local extinction in a given geographic region, are empirically estimated from local observations of species' presence/absence. A connected sampling problem is presented, generalized and solved analytically. Species persistence is shown to provide a direct connection with key spatial macroecological patterns like species-area and endemics-area relationships. Our empirical analysis pertains to two different ecosystems and taxa: a herbaceous plant community and a estuarine fish database. Despite the substantial differences in ecological interactions and spatial scales, we confirm earlier evidence on the general properties of the scaling of persistence times, including the predicted effects of the structure of the spatial interaction network. The framework tested here allows to investigate directly nature and extent of spatial effects in the context of ecosystem dynamics. The notable coherence between spatial and temporal macroecological patterns, theoretically derived and empirically verified, is suggested to underlie general features of the dynamic evolution of ecosystems.

The role of aquatic reservoir fluctuations in long-term cholera patterns.

We propose and analyze an important extension of standard cholera epidemiological models, explicitly accounting for fluctuations of water availability to the human community under study. The seasonality of water input in the reservoir drives the variation of concentration of Vibrio cholerae. Two compartments are added to the Susceptible-Infected-Bacteria model. First, the recovered individuals, which, over many seasons, lose their immunity to the disease and replenish the Susceptible group. Second, the water volume of the reservoir, which determines bacterial dilution and, consequently, the probability of contracting cholera by ingesting contaminated water. By forcing the model with a seasonally varying hydrologic input, we obtain simulations that can be compared to available data for various regions of the World characterized by different hydrological and epidemiological regimes. The model is shown to satisfactorily reproduce important characteristics of disease insurgence and long-term persistence. Using bifurcation analysis of nonlinear systems, we also explore how different degrees of seasonality and values of the basic reproductive number can change the expected long-term epidemiological time series. We find that there exist parametric conditions where the model shows chaotic patterns - i.e. high unpredictability especially in the amplitude of prevalence peaks - which very much resemble actual data on long-term cholera insurgence.

Modelling cholera epidemics: the role of waterways, human mobility and sanitation.

We investigate the role of human mobility as a driver for long-range spreading of cholera infections, which primarily propagate through hydrologically controlled ecological corridors. Our aim is to build a spatially explicit model of a disease epidemic, which is relevant to both social and scientific issues. We present a two-layer network model that accounts for the interplay between epidemiological dynamics, hydrological transport and long-distance dissemination of the pathogen Vibrio cholerae owing to host movement, described here by means of a gravity-model approach. We test our model against epidemiological data recorded during the extensive cholera outbreak occurred in the KwaZulu-Natal province of South Africa during 2000-2001. We show that long-range human movement is fundamental in quantifying otherwise unexplained inter-catchment transport of V. cholerae, thus playing a key role in the formation of regional patterns of cholera epidemics. We also show quantitatively how heterogeneously distributed drinking water supplies and sanitation conditions may affect large-scale cholera transmission, and analyse the effects of different sanitation policies.

On spatially explicit models of cholera epidemics.

We generalize a recently proposed model for cholera epidemics that accounts for local communities of susceptibles and infectives in a spatially explicit arrangement of nodes linked by networks having different topologies. The vehicle of infection (Vibrio cholerae) is transported through the network links that are thought of as hydrological connections among susceptible communities. The mathematical tools used are borrowed from general schemes of reactive transport on river networks acting as the environmental matrix for the circulation and mixing of waterborne pathogens. Using the diffusion approximation, we analytically derive the speed of propagation for travelling fronts of epidemics on regular lattices (either one-dimensional or two-dimensional) endowed with uniform population density. Power laws are found that relate the propagation speed to the diffusion coefficient and the basic reproduction number. We numerically obtain the related, slower speed of epidemic spreading for more complex, yet realistic river structures such as Peano networks and optimal channel networks. The analysis of the limit case of uniformly distributed population sizes proves instrumental in establishing the overall conditions for the relevance of spatially explicit models. To that extent, the ratio between spreading and disease outbreak time scales proves the crucial parameter. The relevance of our results lies in the major differences potentially arising between the predictions of spatially explicit models and traditional compartmental models of the susceptible-infected-recovered (SIR)-like type. Our results suggest that in many cases of real-life epidemiological interest, time scales of disease dynamics may trigger outbreaks that significantly depart from the predictions of compartmental models.

Inferring plant ecosystem organization from species occurrences.

In this paper, we present an approach capable of extracting insights on ecosystem organization from merely occurrence (presence/absence) data. We extrapolate to the collective behavior by encapsulating some simplifying assumptions within a given set of constraints, and then examine their ecological implications. We show that by using the mean occurrence and co-occurrence of species as constraints, one is able to capture detailed statistics of a plant community distributed across a vast semiarid area of the United States. The approach allows us to quantify the species' effective couplings: Their frequencies exhibit a peak at zero and the minimal pairwise model is able to capture about 80% of the ecosystem structure. Our analysis reveals a relatively stronger impact of the species network on uncommon species and underscores the importance of species pairs experiencing positive couplings. Additionally, we study the associations among species and, interestingly, find that the frequencies of groups of different species, which the approach is able to capture, exhibit a power-law-like distribution.

Hydrologic dynamics and ecosystem structure.

Ecohydrology is the science that studies the mutual interaction between the hydrological cycle and ecosystems. Such an interaction is especially intense in water-controlled ecosystems, where water may be a limiting factor, not only because of its scarcity, but also because of its intermittent and unpredictable appearance. Hydrologic dynamics is shown to be a crucial factor for ecological patterns and processes. The probabilistic structure of soil moisture in time and space is presented as the key linkage between soil, climate and vegetation dynamics. Nutrient cycles, vegetation coexistence and plant response to environmental conditions are all intimately linked to the stochastic fluctuation of the hydrologic inputs driving an ecosystem.

Mean first passage times of processes driven by white shot noise.

We consider mean first passage times in systems driven by white shot noise with exponentially distributed jump heights. Simple interpretable results are obtained and the linkage between those results and the steady-state probability density function of the process is presented. The virtual waiting-time or Takács process (constant losses) and the shot noise process with linear losses are analyzed in depth, along with a more complex process with useful implications for the modeling of the soil moisture dynamics in hydrology.

Antibody-induced acute factor X deficiency: clinical manifestations and properties of the antibody.

A patient is described with serious bleeding due to a transient selective deficiency of factor X. Crossed immunoelectrophoresis of patient's plasma with anti-factor X antibody revealed an abnormal factor X arc suggestive of the presence of plasma factor X/anti-factor X immune complexes. A similar abnormal arc was obtained on adding the patient's IgG to normal plasma. Immunoblotting of factor X after reduced SDS-PAGE revealed that the patient's IgG bound to the light chain of intact factor X but not Gla-domainless factor X. The patient's IgG inhibited activation of factor X by VIIa/tissue factor (TF), by IXa/VIIIa/phospholipid complex, and by Russell's viper venom. The IgG failed to inhibit the proteolytic activity of factor Xa towards a chromogenic substrate. However, under reaction conditions of limited factor Xa availability, the IgG could be shown to impair hemostatic functions of factor Xa that require the participation of its light chain: activation of prothrombin by prothrombinase; activation of factor VII bound to TF; and inhibition of VIIa/TF activity by factor Xa/tissue factor pathway inhibitor complexes. A few earlier patients have been described with transient, selective factor X deficiency and serious bleeding, but in only one was evidence obtained of an antibody against factor X. It will be of interest to learn whether use of the techniques described in this report will permit the identification of immunoglobulin with similar binding and functional properties in future patients with this rare syndrome.

The problem of cardiac valve prostheses, anticoagulants, and pregnancy.

To assess the maternal and fetal risks in patients with cardiac valve prostheses, a series of 223 pregnancies in 156 women was studied. In 68 pregnancies (group I) treatment with antiplatelet agents was substituted for that with coumarinics from the first trimester on. Group II (128 pregnancies) received coumarinics through the thirty-eighth week of gestation. Three patients in group I died as a result of thrombosis of their caged-ball valves. The incidence of cerebral embolism was 25.0% in group I and 2.3% in group II patients, while that of spontaneous abortion was 10.3% and 28.1%, respectively. Coumarin embryopathy was found in 7.9% of group II infants. Fetal death did not occur in the 12 cases in which subcutaneous heparin was substituted for the coumarin derivative in the first trimester and the last 2 weeks of pregnancy (group III), but maternal cerebral embolism developed in 8.3% of the patients. Finally, uneventful pregnancies and deliveries were observed in 12 of 15 mothers (group IV) with biological prostheses who received no anticoagulants. It is concluded that (1) women with cardiac valve prostheses should be counseled against becoming pregnant, (2) antiplatelet agents do not provide protection against thromboembolism in these patients, (3) because of the high incidence of fetal death and birth defects use of coumarinics is contraindicated in the first trimester and the last weeks of pregnancy, (4) the substitution of heparin at these times may decrease the incidence of these complications, and (5) bioprostheses are indicated in women who wish to bear children.

[Coronary thrombolysis in acute myocardial infarction. Initial experience with an intravenous thrombolytic agent]. / Trombolisis coronaria en el infarto agudo del miocardio. Experiencia inicial con un agente trombolítico intravenoso.

Thirteen patients with less than 5 hours of the onset of symptoms of acute myocardial infarction underwent selective coronary angiography. Ten of them had angiographic signs of coronary thrombosis. In these ten patients 15 mgs of an acylated streptokinase-plasminogen complex (BRL 26921 Beecham Farmaceuticals) were administered intravenously. Total angiographic recanalization was observed in 7 patients. The coronary arteries involved were the left anterior descending in 4 cases and the right coronary artery in 3. In 8 out of the 10 patients significant diminution of injury pattern in EKG was registered, however in all of them the necrosis pattern supervened. Prolongation of the thrombin and thromboplastin times, as well as an important fibrinogen disminution were documented in all instances. There were not complications related to the administration of the drug. An increase of muscle enzimes was documented in all cases. The follow-up was uneventfull with excellent results in all the patients. This study proves that with IV trombolitic therapy coronary recanalization can be achieved in the mayority of the patients; however there is no question that myocardial infarction finally ocurred. We speculate about the possibility of avoiding infarction by the administration of the drug within the first hour after the onset of the symptoms.